The microbiology and pathogenesis of nonfermenting Gram-negative infections

Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B.cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B.cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6].no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g.neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1).As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g.sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g.water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1].These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.Purpose of reviewThis review provides an overview of most recent evidence about pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant nonfermenting Gram-negative bacteria (NFGNB).The growing clinical importance of NFGNB as important opportunistic pathogens causing difficult-to-treat infections in a fragile patients' population in stressed by numerous studies. Identification of novel virulence factors and deciphering of their mechanisms of action have greatly furthered our understanding of NFGNB pathogenesis, revealing that each pathogen-specific armamentarium of virulence factors (adhesins, motility, capsule, biofilm, lipopolysaccharide, exotoxins, exoenzymes, secretion systems, siderophores) can be likely responsible for the difference in the pathophysiology even in the context of a similar infection site. Emerging evidence of the immunomodulatory effect of some virulence factors is also acknowledged.NFGNB continue to be a serious global problem as cause of life-threatening opportunistic infections, owing to a highly heterogeneous content of virulence factors and their extensive number of intrinsic resistance mechanisms. Further efforts in development of novel effective antimicrobials and of alternative strategies targeting key virulence factors are warranted.Papers of particular interest, published within the annual period of review, have been highlighted as:Nonfermenting Gram-negative bacilli (NFGNB) are a group of taxonomically heterogeneous aerobic, nonspore-forming bacilli that are unable to ferment carbohydrates and derive energy by using simple carbohydrates in an oxidative fashion [1]. These organisms are ubiquitously distributed in the environment as saprophytes, typically inhabiting moist ecosystems (e.g. water, soil, plants), and some are recognized as member of the healthy human gut microbiota [2-4].Over past decades, however, NFGNB have emerged as important nosocomial pathogens, owing to their ability to persist in the hospital environment (e.g. sinks, respirators, nebulizers, dialysate, saline, catheters and other devices surfaces) and intrinsic antimicrobial resistance phenotypes (Table 1). As such, this group of microorganisms is increasingly recognized as cause of difficult-to-treat, life-threatening infections in fragile patients [e.g. neutropenic and intensive care unit patients, cystic fibrosis (CF)] [5], being a prevalent cause of nosocomial pneumonia and secondary bacteraemia (which can also develop from contaminated health-care equipment and surgical site infections) [6]. no caption availableOverview of virulence factors and intrinsic antimicrobial resistance profiles of P. aeruginosa, S. maltophilia, A. baumannii, B. cepacia complexAMP, ampicillin; AMX, amoxicillin; AMC, ampicillin/clavulanic acid; AMS, ampicillin/sulbactam; TIC, ticarcillin; TIM, ticarcillin/clavulanic acid; PIP, piperacillin; TZP, piperacillin/tazobactam; IMI, imipenem; MEM, meropenem; AZT, aztreonam; CTX, cefotaxime; CRO, ceftriaxone; ETP, ertapenem; CM, chloramphenicol; TET, tetracycline; TIG, tigecycline; TMP, trimethoprim; KAN, kanamycin; AGs: all aminoglycosides; FOS, Fosfomycin; CIP, ciprofloxacin; COL, colistin; OMVs: outer-membrane vescicles; LPS, lipopolysaccharide.A. baumannnii, A. pittii, A. nosocomialis.Here, we provide an overview of the pathogenesis traits and virulence factors contributing to successful colonization or infection by P. aeruginosa, A. baumannii, S. maltophilia and B. cepacia complex, among the most clinically relevant NFGNB.