scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Acinetobacter baumannii: Human infections, factors contributing to pathogenesis and animal models

01 Mar 2013-Fems Microbiology Reviews (FEMS Microbiol Rev)-Vol. 37, Iss: 2, pp 130-155
TL;DR: This review summarizes the characteristics of A. baumannii that contribute to its pathogenesis, with a focus on motility, adherence, biofilm formation, and iron acquisition.
Abstract: Acinetobacter baumannii has emerged as a medically important pathogen because of the increasing number of infections produced by this organism over the preceding three decades and the global spread of strains with resistance to multiple antibiotic classes. In spite of its clinical relevance, until recently, there have been few studies addressing the factors that contribute to the pathogenesis of this organism. The availability of complete genome sequences, molecular tools for manipulating the bacterial genome, and animal models of infection have begun to facilitate the identification of factors that play a role in A. baumannii persistence and infection. This review summarizes the characteristics of A. baumannii that contribute to its pathogenesis, with a focus on motility, adherence, biofilm formation, and iron acquisition. In addition, the virulence factors that have been identified to date, which include the outer membrane protein OmpA, phospholipases, membrane polysaccharide components, penicillin-binding proteins, and outer membrane vesicles, are discussed. Animal models systems that have been developed during the last 15 years for the study of A. baumannii infection are overviewed, and the recent use of these models to identify factors involved in virulence and pathogenesis is highlighted.
Citations
More filters
Journal ArticleDOI
TL;DR: The recent expansion of A. baumannii sequenced genomes has permitted the development of large-array phylogenomic and phenotypic analyses, which can offer valuable insights into the evolution and adaptation of the human pathogen.
Abstract: Acinetobacter baumannii is an opportunistic nosocomial pathogen and one of the six most important multidrug-resistant microorganisms in hospitals worldwide. This human pathogen is responsible for a vast array of infections, of which ventilator-associated pneumonia and bloodstream infections are the most common, and mortality rates can reach 35%. Community-acquired infections have also been reported, but few strains have been recovered from environmental sources and infection reservoirs external to the hospital have not been identified. The majority of A. baumannii infections are caused by two main population clones with worldwide distribution. Infection outbreaks are often associated with multidrug resistance, including the recent emergence of strains resistant to all available antibiotics. Nevertheless, A. baumannii virulence traits and pathogenic potential have mostly remained elusive. The recent expansion of A. baumannii sequenced genomes has permitted the development of large-array phylogenomic and phenotypic analyses, which can offer valuable insights into the evolution and adaptation of A. baumannii as a human pathogen. This review summarises these recent advances, with particular focus on A. baumannii evolutionary and genomic aspects, and proposes new avenues of research.

626 citations

Journal ArticleDOI
TL;DR: Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp.
Abstract: Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)-Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

618 citations


Cites methods from "Acinetobacter baumannii: Human infe..."

  • ...genus’ putative virulence factors (60, 93)....

    [...]

  • ...baumannii infection, artificial models have been used, such as infecting mice intraperitoneally (a clinically irrelevant route of entry) or mixing the inoculum with porcine mucin as a foreign body that inhibits the host’s immune system from rapidly clearing the organism (59, 60)....

    [...]

Journal ArticleDOI
TL;DR: Current studies on the virulence factors that contribute to A. baumannii pathogenesis are summarized and Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites are discussed.
Abstract: Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of -lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

572 citations


Cites background or result from "Acinetobacter baumannii: Human infe..."

  • ...baumannii, compared to those in other Gram-negative pathogens (McConnell et al., 2013)....

    [...]

  • ...In A. baumannii, OmpA is the very well-characterized virulence factor with a variety of interesting biological properties identified in in vitro model systems (Smith et al., 2007; McConnell et al., 2013)....

    [...]

  • ...Although recent genomic and phenotypic analyses of A. baumannii have identified several virulence factors responsible for its pathogenicity, relatively few virulence factors have been identified in A. baumannii, compared to those in other Gram-negative pathogens (McConnell et al., 2013)....

    [...]

  • ...Many reports have shown that A. baumannii rapidly develops resistance to antimicrobials, and multidrug-resistant strains have been isolated (McConnell et al., 2013)....

    [...]

  • ...baumannii, OmpA is the very well-characterized virulence factor with a variety of interesting biological properties identified in in vitro model systems (Smith et al., 2007; McConnell et al., 2013)....

    [...]

Journal ArticleDOI
TL;DR: Among many of the pathogenic bacteria, OmpA proteins have important pathogenic roles including bacterial adhesion, invasion, or intracellular survival as well as evasion of host defenses or stimulators of pro-inflammatory cytokine production.

240 citations

Journal ArticleDOI
TL;DR: This review discusses the multi-drug resistant Gram-negative pathogens of highest critical priority and summarizes the current state-of-the-art in phage therapy targeting these organisms.
Abstract: Increasing reports of antimicrobial resistance and limited new antibiotic discoveries and development have fuelled innovation in other research fields and led to a revitalization of bacteriophage (phage) studies in the Western world. Phage therapy mainly utilizes obligately lytic phages to kill their respective bacterial hosts, while leaving human cells intact and reducing the broader impact on commensal bacteria that often results from antibiotic use. Phage therapy is rapidly evolving and has resulted in cases of life-saving therapeutic use and multiple clinical trials. However, one of the biggest challenges this antibiotic alternative faces relates to regulations and policy surrounding clinical use and implementation beyond compassionate cases. This review discusses the multi-drug resistant Gram-negative pathogens of highest critical priority and summarizes the current state-of-the-art in phage therapy targeting these organisms. It also examines phage therapy in humans in general and the approaches different countries have taken to introduce it into clinical practice and policy. We aim to highlight the rapidly advancing field of phage therapy and the challenges that lie ahead as the world shifts away from complete reliance on antibiotics.

219 citations

References
More filters
Journal ArticleDOI
21 May 1999-Science
TL;DR: Improvements in understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.
Abstract: Bacteria that attach to surfaces aggregate in a hydrated polymeric matrix of their own synthesis to form biofilms. Formation of these sessile communities and their inherent resistance to antimicrobial agents are at the root of many persistent and chronic bacterial infections. Studies of biofilms have revealed differentiated, structured groups of cells with community properties. Recent advances in our understanding of the genetic and molecular basis of bacterial community behavior point to therapeutic targets that may provide a means for the control of biofilm infections.

11,162 citations


"Acinetobacter baumannii: Human infe..." refers background in this paper

  • ...baumannii to biotic and abiotic surfaces results in the development of biofilms, which are complex multicellular three-dimensional structures with cells in intimate contact with each other and encased in an extra-cellular matrix that can be comprised of carbohydrates, nucleic acids, proteins, and other macromolecules (Costerton et al., 1999)....

    [...]

  • ...…in the development of biofilms, which are complex multicellular three-dimensional structures with cells in intimate contact with each other and encased in an extra-cellular matrix that can be comprised of carbohydrates, nucleic acids, proteins, and other macromolecules (Costerton et al., 1999)....

    [...]

Journal ArticleDOI
TL;DR: It is understood that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health, and that treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.
Abstract: Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.

5,748 citations

Journal ArticleDOI
TL;DR: The proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals, and in neutropenic patients, infections with Candida species, enterococci, and viridans group streptococci were significantly more common.
Abstract: Background. Nosocomial bloodstream infections (BSIs) are important causes of morbidity and mortality in the United States. Methods. Data from a nationwide, concurrent surveillance study (Surveillance and Control of Pathogens of Epidemiological Importance [SCOPE]) were used to examine the secular trends in the epidemiology and microbiology of nosocomial BSIs. Results. Our study detected 24,179 cases of nosocomial BSI in 49 US hospitals over a 7-year period from March 1995 through September 2002 (60 cases per 10,000 hospital admissions). Eighty-seven percent of BSIs were monomicrobial. Gram-positive organisms caused 65% of these BSIs, gram-negative organisms caused 25%, and fungi caused 9.5%. The crude mortality rate was 27%. The most-common organisms causing BSIs were coagulasenegative staphylococci (CoNS) (31% of isolates), Staphylococcus aureus (20%), enterococci (9%), and Candida species (9%). The mean interval between admission and infection was 13 days for infection with Escherichia coli, 16 days for S. aureus, 22 days for Candida species and Klebsiella species, 23 days for enterococci, and 26 days for Acinetobacter species. CoNS, Pseudomonas species, Enterobacter species, Serratia species, and Acinetobacter species were more likely to cause infections in patients in intensive care units ( ). In neutropenic patients, infections P ! .001 with Candida species, enterococci, and viridans group streptococci were significantly more common. The proportion of S. aureus isolates with methicillin resistance increased from 22% in 1995 to 57% in 2001 ( , trend P ! .001 analysis). Vancomycin resistance was seen in 2% of Enterococcus faecalis isolates and in 60% of Enterococcus faecium isolates. Conclusion. In this study, one of the largest multicenter studies performed to date, we found that the proportion of nosocomial BSIs due to antibiotic-resistant organisms is increasing in US hospitals.

4,084 citations


"Acinetobacter baumannii: Human infe..." refers background in this paper

  • ...Acinetobacter baumannii is also a common cause of bloodstream infections in the intensive care setting (Wisplinghoff et al., 2004)....

    [...]

  • ...Crude mortality rates for A. baumannii bloodstream infections have been reported to be between 28% and 43% (Seifert et al., 1995; Wisplinghoff et al., 2004)....

    [...]

  • ...While these studies provide important information regarding the epidemiology and clinical management of A. baumannii infections, they do not address the underlying biological basis for the increasing success of this organism as a human pathogen....

    [...]

Journal ArticleDOI
TL;DR: This review details the significant advances that have been made in understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.
Abstract: Acinetobacter baumannii has emerged as a highly troublesome pathogen for many institutions globally. As a consequence of its immense ability to acquire or upregulate antibiotic drug resistance determinants, it has justifiably been propelled to the forefront of scientific attention. Apart from its predilection for the seriously ill within intensive care units, A. baumannii has more recently caused a range of infectious syndromes in military personnel injured in the Iraq and Afghanistan conflicts. This review details the significant advances that have been made in our understanding of this remarkable organism over the last 10 years, including current taxonomy and species identification, issues with susceptibility testing, mechanisms of antibiotic resistance, global epidemiology, clinical impact of infection, host-pathogen interactions, and infection control and therapeutic considerations.

2,915 citations


"Acinetobacter baumannii: Human infe..." refers background or result in this paper

  • ...A subsequent study demonstrated that A. baumannii reduced the ability of C. albicans to kill C. elegans during co-infection, demonstrating that this model can be used to study eukaryote–prokaryote interactions (Peleg et al., 2008b)....

    [...]

  • ...…heme, a host product that could be available to bacteria at sites where extensive cell and tissue damage are produced by infections such as necrotizing fasciitis (Brachelente et al., 2007; Charnot-Katsikas et al., 2009; Corradino et al., 2010) or in severely injured patients (Peleg et al., 2008a)....

    [...]

  • ...There are a number of reviews that provide comprehensive information on antibiotic resistance mechanisms and clinical aspects of A. baumannii infection (Chopra et al., 2008; Peleg et al., 2008a; Vila & Pachón, 2008; Fishbain & Peleg, 2010; Gordon & Wareham, 2010) ....

    [...]

Journal ArticleDOI
TL;DR: An overview of the current knowledge of the genus Acinetobacter is presented, with the emphasis on the clinically most important species, Acetobacter baumannii.
Abstract: Since the 1970s, the spread of multidrug-resistant (MDR) Acinetobacter strains among critically ill, hospitalized patients, and subsequent epidemics, have become an increasing cause of concern. Reports of community-acquired Acinetobacter infections have also increased over the past decade. A recent manifestation of MDR Acinetobacter that has attracted public attention is its association with infections in severely injured soldiers. Here, we present an overview of the current knowledge of the genus Acinetobacter, with the emphasis on the clinically most important species, Acinetobacter baumannii.

1,558 citations


"Acinetobacter baumannii: Human infe..." refers background in this paper

  • ...…that persists on contaminated hospital equipment or by contact with healthcare personnel that have been exposed to the organism through contact with a colonized patient (Maragakis et al., 2004; Crnich et al., 2005; Dijkshoorn et al., 2007; Asensio et al., 2008; Rodrı́guez-Baño et al., 2009)....

    [...]

  • ...baumannii results from colonization of the airway via environmental exposure, which is followed by the development of pneumonia (Dijkshoorn et al., 2007)....

    [...]

  • ...It is thought that ventilator-associated pneumonia caused by A. baumannii results from colonization of the airway via environmental exposure, which is followed by the development of pneumonia (Dijkshoorn et al., 2007)....

    [...]

  • ...baumannii that persists on contaminated hospital equipment or by contact with healthcare personnel that have been exposed to the organism through contact with a colonized patient (Maragakis et al., 2004; Crnich et al., 2005; Dijkshoorn et al., 2007; Asensio et al., 2008; Rodrı́guez-Baño et al., 2009)....

    [...]