Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii

Eijkelkamp, Bart A.; Stroeher, Uwe H.; Hassan, Karl A.; Paulsen, Ian T.; Brown, Melissa H.

doi:10.1186/1471-2164-15-1020

Cited by 98 publications

(107 citation statements)

References 96 publications

(109 reference statements)

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“…Additionally, the two-component regulatory system BfmRS is involved in Csu expression, as a bfmR mutant did not express CsuA/B and was unable to form biofilms (6). Interestingly, previous genome sequence analyses suggested that other A. baumannii strains, including the commonly used ATCC 17978 (17978) strain, encode a nonfunctional Csu operon due to inactivating single-nucleotide polymorphisms (9,10). However, those observations have not been phenotypically confirmed.…”

mentioning

confidence: 76%

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Moon

Weber

Feldman

2017

Antimicrob Agents Chemother

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Acinetobacter baumannii is emerging as a multidrug-resistant nosocomial pathogen of increasing threat to human health worldwide. Pili are important bacterial virulence factors, playing a role in attachment to host cells and biofilm formation. The Csu pilus, which is assembled via the chaperone-usher secretion system, has been studied in A. baumannii ATCC 19606. Here we show that, in opposition to previous reports, the common laboratory strain ATCC 17978 produces Csu pili. We found that, although ATCC 17978 was resistant to sulfamethoxazole (Smx) and trimethoprim (Tmp), subinhibitory concentrations of these antibiotics abolished the expression of Csu and consequently produced a dramatic reduction in biofilm formation by ATCC 17978. Smx and Tmp acted synergistically to inhibit the enzymatic systems involved in the bacterial synthesis of tetrahydrofolate (THF), which is required for the synthesis of nucleotides. The effects of these antibiotics were partially relieved by exogenous THF addition, indicating that Smx and Tmp turn off Csu assembly by inducing folate stress. We propose that, for Acinetobacter, nanomolar concentrations of Smx and Tmp represent a "danger signal." In response to this signal, Csu expression is repressed, allowing biofilm dispersal and escape from potentially inhibitory concentrations of antibiotics. The roles of antibiotics as signaling molecules are being increasingly acknowledged, with clear implications for both the treatment of bacterial diseases and the understanding of complex microbial interactions in the environment.KEYWORDS Acinetobacter, folate biosynthesis, folate stress, pilus assembly P ili formed by Gram-negative bacteria play an important role in the ability of these organisms to adhere to surfaces, to form biofilms, and to invade host cells and can affect motility (1). The chaperone-usher (CU) family of pili has been the focus of many studies, and the P-pili and type I pili of uropathogenic Escherichia coli play particularly important roles in establishing infection (2-4). A CU pathway for pilus biogenesis is present in most medically relevant Acinetobacter species (5). The genes for this CU pathway are encoded in a single six-gene operon, termed csu, and include csuA /B, csuA, csuB, csuC, csuD, and csuE (6). In the presence of the CsuC chaperone, CsuA/B polymerizes to form the major pilus subunit (7). Additional experimental and bioinformatic analyses have provided evidence that CsuD functions as the usher and CsuE as a tip adhesin, while CsuA and CsuB may play roles as minor pilin subunits (5,6,8). Despite its being conserved in many sequenced Acinetobacter baumannii strains, the role of Csu has been characterized only for A. baumannii ATCC 19606, an isolate used in many laboratories (5, 6). Genetic studies in this strain have shown that mutation of csuC or

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mentioning

confidence: 76%

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Moon

Weber

Feldman

2017

Antimicrob Agents Chemother

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“…Another study found that the CsuA/B pilin subunit was the most abundant protein identified within the pellicle matrix of multiple A. baumannii strains (61), further strengthening the role of Csu pili in biofilm formation and maintenance. Previous reports also identified a single nucleotide insertion in the csuB gene of A. baumannii ATCC 17978, suggesting that this system may be nonfunctional in this strain (62,63); however, recent resequencing of the A. baumannii ATCC 17978 genome (GenBank accession no. CP012004) did not find the same insertion event (64).…”

Section: Cell Surfacementioning

confidence: 95%

“…CP012004) did not find the same insertion event (64). Lastly, other chaperone/usher pilus-like systems have been bioinformatically identified in many A. baumannii strains, but none of those systems has been functionally characterized (61,62). Mass spectrometric characterization of pellicle-associated proteins did find that non-Csu-pilin subunits were present, indicating that these systems may be functional.…”

Section: Cell Surfacementioning

confidence: 97%

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2016

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The genus Acinetobacter encompasses multiple nosocomial opportunistic pathogens that are of increasing worldwide relevance because of their ability to survive exposure to various antimicrobial and sterilization agents. Among these, Acinetobacter baumannii, Acinetobacter nosocomialis, and Acinetobacter pittii are the most frequently isolated in hospitals around the world. Despite the growing incidence of multidrug-resistant Acinetobacter spp., little is known about the factors that contribute to pathogenesis. New strategies for treating and managing infections caused by multidrug-resistant Acinetobacter strains are urgently needed, and this requires a detailed understanding of the pathobiology of these organisms. In recent years, some virulence factors important for Acinetobacter colonization have started to emerge. In this review, we focus on several recently described virulence factors that act at the bacterial surface level, such as the capsule, O-linked protein glycosylation, and adhesins. Furthermore, we describe the current knowledge regarding the type II and type VI secretion systems present in these strains.

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“…A. baumannii adherence to host cells is mediated by fimbria or OmpA (1,15). The exact mechanism of adherence of clinical A. baumannii isolates to various biotic or abiotic surfaces is not understood so far suggesting the possession of various independent molecular mechanisms for adherence to such surfaces by A. baumannii (16). It is reported that pili play an important role in twitching motility as well as adhesion and biofilm formation (17).…”

Section: Introductionmentioning

confidence: 99%

Correlation of Virulence Factors and Cell Adhesion of Clinical Isolates of Acinetobacter baumannii

Payam

Rasooli

Owlia

et al. 2018

Arch Clin Infect Dis

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Background: Adhesion to host cells is an important and critical feature of Acinetobacter baumannii pathogenesis. OmpA, ABAYE1319-CsuA/b, and ABAYE2132 are highly prevalent and conserved fimbrial proteins; ABAYE1859 and ABAYE0304 fimbrial antigens are the factors described as novel vaccine candidates against multidrug-resistant (MDR) A. baumannii. Methods: The current study aimed at investigating the significance of A. baumannii fimbrial and outer membrane proteins A (OmpA) in adherence to human epithelial cells. Antibiotic resistance was determined by the broth microdilution method. Phenotypic identification of isolates producing ESBL (extended-spectrum beta-lactamase) was conducted using double-disc synergy test (DDST). The virulence factors were detected by the polymerase chain reaction (PCR) in 100 non duplicate clinical isolates of A. baumannii; 18 clinical isolates were selected for adhesion assay based on antibiotic resistance and PCR results. Results: The current study results showed that ABAYE2132, ABAYE0304, and ABAYE1319-CsuA/B had significant correlation with cell

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Comparative analysis of surface-exposed virulence factors of Acinetobacter baumannii

Cited by 98 publications

References 96 publications

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Subinhibitory Concentrations of Trimethoprim and Sulfamethoxazole Prevent Biofilm Formation by Acinetobacter baumannii through Inhibition of Csu Pilus Expression

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

Correlation of Virulence Factors and Cell Adhesion of Clinical Isolates of Acinetobacter baumannii

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