1671A Fatal Outbreak of a Rare but Emerging Clone of Extensively Drug-resistant Acinetobacter baumannii with Enhanced Virulence

Jones, Crystal L.; Clancy, Megan; Singh, Shweta; Honnold, Cary L.; Snesrud, Erik; McGann, Patrick; Onmus-Leone, Fatma; Ong, Ana; Kwak, Yoon I.; Waterman, Paige; Zurawski, Daniel V.; Clifford, Robert; Lesho, Emil

doi:10.1093/ofid/ofu052.1217

Cited by 25 publications

(41 citation statements)

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“…Harris et al (2013) also reported the highly virulent LAC-4 strain, and infection with this strain resulted in all C57BL/6 and BAMH/C mice dying within 48 h at a dose of 10 8 colony-forming units (CFU) [4]. Jones et al (2015) also reported some highly virulent strains that were 10 to 100 times more concentrated in the lungs of infected mice than normal strains [5]. In China, there have also been reports of highly virulent strains.…”

Section: Introductionmentioning

confidence: 99%

Wza gene knockout decreases Acinetobacter baumannii virulence and affects Wzy-dependent capsular polysaccharide synthesis

et al. 2019

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To investigate the virulence of capsular polysaccharide export protein (Wza) in carbapenemresistant Acinetobacter baumannii and its effect on capsule formation. wza gene knockout and complementation strains were constructed, and changes in bacterial virulence were observed using in vitro adhesion, antiserum complement killing, anti-oxidation experiments, and infections in Galleria mellonella and mice. The effect of wza knockout on the genes wzb and wzc and wzi were assessed by RT-PCR. We successfully constructed wza knockout and complementation strains. Compared with wildtype (WT) strains, wza knockout strains displayed lower adhesion to A549 cells (p = 0.044), lower antiserum complement killing ability (p = 0.001), and lower mortality of G. mellonella (p = 0.010) and mice (p = 0.033). Expression levels of wzb, wzc and wzi were decreased in wza knockout strains. The antioxidant capacity of Wza knockout bacteria was only slightly decreased. Complementation of the wza gene returned the adhesion ability, antiserum complement killing ability, and mortality of G. mellonella and mice to WT levels. Expression of wzb, wzc and wzi was also returned to WT levels following wza complementation. The results clearly demonstrate that Wza is toxic. Wza affects the expression of other proteins of the Wzy capsule polysaccharide synthesis pathway, which affects the assembly, export, and extracellular fixation of capsular polysaccharide, resulting in synergistic effects that decrease bacterial virulence.

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Section: Introductionmentioning

confidence: 99%

Wza gene knockout decreases Acinetobacter baumannii virulence and affects Wzy-dependent capsular polysaccharide synthesis

et al. 2019

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“…The related question of why Acinetobacter pilA genes have diverged into glycosylated and non-glycosylated forms is complicated by the fact that no functional gain or defect has been attributed to the C-terminal glycan in Acinetobacter, and both tfpOϪ and tfpOϩ strains have been shown to be infectious (72,73). Similar results were obtained for the ⌬tfpO mutant of P. aeruginosa 1244, which was also found to be equally susceptible to phage attachment (21).…”

Section: Discussionmentioning

confidence: 86%

Structural Diversity in the Type IV Pili of Multidrug-resistant Acinetobacter

Piepenbrink

Lillehoj

Harding

et al. 2016

Journal of Biological Chemistry

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Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections. A. baumannii expresses a variety of virulence factors, including type IV pili, bacterial extracellular appendages often essential for attachment to host cells. Here, we report the high resolution structures of the major pilin subunit, PilA, from three Acinetobacter strains, demonstrating that A. baumannii subsets produce morphologically distinct type IV pilin glycoproteins. We examine the consequences of this heterogeneity for protein folding and assembly as well as host-cell adhesion by Acinetobacter. Comparisons of genomic and structural data with pilin proteins from other species of soil gammaproteobacteria suggest that these structural differences stem from evolutionary pressure that has resulted in three distinct classes of type IVa pilins, each found in multiple species.Type IV pili are extracellular adhesive appendages primarily comprising a single protein subunit, called the major pilin, which is assembled into a narrow (ϳ6 -9-nm) helical fiber of variable length (up to 2.5 m) (1). One or more other proteins, called minor pilins, are also incorporated into the fiber at low levels. All pilins contain an N-terminal signal sequence followed by an ϳ30-amino acid hydrophobic ␣-helix resembling a transmembrane domain (the ␣1-N domain). This is, in turn, followed by a soluble ϳ15-kDa globular domain referred to as the pilin headgroup; the hydrophobic helical regions are buried together in the center of the fiber, whereas portions of the C-terminal headgroup are exposed (2, 3).Type IV pili are found in both Gram-negative (4, 5) and Gram-positive (6 -8) bacteria as well as Archea (9). They are involved in a wide range of processes, including twitching motility (10), horizontal gene transfer (11), host-cell adhesion (12), and microcolony/biofilm formation (13). This functional diversity is reflected in the sequence of the pilin proteins that typically have little or no sequence identity beyond the hydrophobic portion of the N-terminal ␣-helix. This lack of sequence identity is apparent even in cases where there is high structural similarity.In contrast, within a given species, the minor pilins are typically well conserved. Only the major pilin is highly variable (14 -16) and then only in those regions left exposed in the assembled pilus (17). This sequence diversity may result from diversifying selection as a mechanism by which to avoid detection by the host immune system (18). However, such diversity can also be found in species whose life cycle is primarily environmental (19). Glycosylation is an additional source of variability in some type IV pilins; O-linked glycosylation has been observed in multiple strains of both Pseudomonas aeruginosa (20 -22) and Neisseria (23,24). Additional glycosylation sites have been found in class II strains of Neisseria meningitidis where they have been hypothesized to play a role in immune evasion (25).Among the man...

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“…43,66,67 Acquisition and spread of ABC has been noted in hospitals, 66 rehabilitation centers, and long-term care facilities (LTCFs), among pilgrims returning from the Hajj (Makkah) 68 and in the community (particularly among the elderly). 1,2 Colonized or infected patients, selection pressure from antimicrobial use, and incomplete compliance with infection control procedures may facilitate persistence or spread of MDR-ABC within hospital or institutional settings. 1,66 Removal or disinfection and sterilization of contaminated equipment (e.g., ventilator or nebulizer tubing) or fomites may eliminate the problem.…”

Section: Hospital-acquired Pneumoniamentioning

confidence: 99%

Infections Due to Acinetobacter baumannii in the ICU: Treatment Options

Lynch

Zhanel

Clark

2017

Semin Respir Crit Care Med

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Bacteria within the genus (principally- complex [ABC]) are gram-negative coccobacilli that may cause nosocomial infections in critically ill or debilitated patients (particularly ventilator-associated pneumonia and infections of the bloodstream, urinary tract, and wounds). Treatment of infections is difficult, as spp. are resistant to multiple antimicrobial agents, and have a remarkable ability to via mechanisms that include plasmids, transposons, integrons, and resistance islands. Since the 1990s, global resistance to antimicrobials has escalated dramatically among ABC. Global spread of multidrug-resistant (MDR)- strains reflects dissemination of a few clones between hospitals, geographic regions, and continents; excessive use of antibiotics amplifies this spread. Many isolates are resistant to all antimicrobials except colistin (polymyxin E) and tigecycline, and some infections are untreatable with existing antimicrobial agents. Antimicrobial resistance poses a serious threat to treat or prevent infections due to ABC. Strategies to curtail environmental colonization with MDR-ABD will require aggressive infection control efforts and cohorting of infected patients. Thoughtful antibiotic strategies are essential to limit the spread of MDR-ABC. Optimal therapy will likely require combination antimicrobial therapy of existing antibiotics as well as development of novel antibiotic classes.

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1671A Fatal Outbreak of a Rare but Emerging Clone of Extensively Drug-resistant Acinetobacter baumannii with Enhanced Virulence

Cited by 25 publications

References 0 publications

Wza gene knockout decreases Acinetobacter baumannii virulence and affects Wzy-dependent capsular polysaccharide synthesis

Wza gene knockout decreases Acinetobacter baumannii virulence and affects Wzy-dependent capsular polysaccharide synthesis

Structural Diversity in the Type IV Pili of Multidrug-resistant Acinetobacter

Infections Due to Acinetobacter baumannii in the ICU: Treatment Options

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