Identification and Characterization of a Glycosyltransferase Involved in
            <i>Acinetobacter baumannii</i>
            Lipopolysaccharide Core Biosynthesis

Luke, Nicole R.; Sauberan, Shauna L.; Russo, Thomas A.; Beanan, Janet M.; Olson, Ruth; Loehfelm, Thomas W.; Cox, Andrew D.; Michael, Frank St.; Vinogradov, Evgeny; Campagnari, Anthony A.

doi:10.1128/iai.00016-10

Cited by 104 publications

(94 citation statements)

References 44 publications

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“…To investigate whether the structural features of the 5= UTR have a regulatory role in cis on recA expression, a low-copy-number plasmid translational reporter was constructed in pNLAC1 (36), in which the recA promoter, 5= UTR, and recA ribosomal start site were fused to the far-red fluorescent protein mKate2. The sequences flanking the recA gene coding sequence were included to maintain sequence context next to the 5= UTR.…”

Section: Resultsmentioning

confidence: 99%

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation

et al. 2017

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In the nosocomial opportunistic pathogen Acinetobacter baumannii, RecAdependent mutagenesis, which causes antibiotic resistance acquisition, is linked to the DNA damage response (DDR). Notably, unlike the Escherichia coli paradigm, recA and DDR gene expression in A. baumannii is bimodal. Namely, there is phenotypic variation upon DNA damage, which may provide a bet-hedging strategy for survival. Thus, understanding recA gene regulation is key to elucidate the yet unknown DDR regulation in A. baumannii. Here, we identify a structured 5= untranslated region (UTR) in the recA transcript which serves as a cis-regulatory element. We show that a predicted stem-loop structure in this 5= UTR affects mRNA half-life and underlies bimodal gene expression and thus phenotypic variation in response to ciprofloxacin treatment. We furthermore show that the stem-loop structure of the recA 5= UTR influences intracellular RecA protein levels and, in vivo, impairing the formation of the stem-loop structure of the recA 5= UTR lowers cell survival of UV treatment and decreases rifampin resistance acquisition from DNA damage-induced mutagenesis. We hypothesize that the 5= UTR allows for stable recA transcripts during stress, including antibiotic treatment, enabling cells to maintain suitable RecA levels for survival. This innovative strategy to regulate the DDR in A. baumannii may contribute to its success as a pathogen.IMPORTANCE Acinetobacter baumannii is an opportunistic pathogen quickly gaining antibiotic resistances. Mutagenesis and antibiotic resistance acquisition are linked to the DNA damage response (DDR). However, how the DDR is regulated in A. baumannii remains unknown, since unlike most bacteria, A. baumannii does not follow the regulation of the Escherichia coli paradigm. In this study, we have started to uncover the mechanisms regulating the novel A. baumannii DDR. We have found that a cisacting 5= UTR regulates recA transcript stability, RecA protein levels, and DNA damage-induced phenotypic variation. Though 5= UTRs are known to provide stability to transcripts in bacteria, this is the first example in which it regulates a bimodal DDR response through recA transcript stabilization, potentially enabling cells to have enough RecA for survival and genetic variability.KEYWORDS Acinetobacter, DNA damage, microbial genetics, RecA, gene expression, molecular biology A cinetobacter baumannii is a Gram-negative opportunistic pathogen that is a major problem in hospitals due to its ability to withstand desiccation (1), allowing it to ultimately reach immunocompromised individuals and cause diseases, including pneumonia and meningitis (2-4). Compounding this problem is the ability of A. baumannii to rapidly gain antibiotic resistances, such that there are now pan-resistant strains (5, 6). This may in part be due to A. baumannii's improved fitness during stress (7-10). However, fully understanding how A. baumannii rapidly acquires antibiotic resistances

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Section: Resultsmentioning

confidence: 99%

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation

et al. 2017

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“…The studies concerning the role of A. baumannii LPS indicated the contribution of the surface carbohydrates residues in the virulence [22]. The endotoxins are also considered as a potent stimulators of inflammatory signalling in human monocytic cells, dependent on both TLR2 (toll-like receptor) and TLR4 receptors.…”

Section: Virulence Factorsmentioning

confidence: 99%

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Nowak

Paluchowska

2015

Folia Histochem Cytobiol.

107

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Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase-negative coccobacillus, most commonly associated with the hospital settings. The ability to survive in adverse environmental conditions as well as high level of natural and acquired antimicrobial resistance make A. baumannii one of the most important nosocomial pathogens. While carbapenems have long been considered as antimicrobials of last-resort, the rates of clinical A. baumannii strains resistant to these antibiotics are increasing worldwide. Carbapenem resistance among A. baumannii is conferred by coexisting mechanisms including: decrease in permeability of the outer membrane, efflux pumps, production of beta-lactamases, and modification of penicillin-binding proteins. The most prevalent mechanism of carbapenem resistance among A. baumannii is associated with carbapenem-hydrolysing enzymes that belong to Ambler class D and B beta-lactamases. In addition, there have also been reports of resistance mediated by selected Ambler class A carbapenemases among A. baumannii strains. Resistance determinants in A. baumannii are located on chromosome and plasmids, while acquisition of new mechanisms can be mediated by insertion sequences, integrons, transposons, and plasmids. Clinical relevance of carbapenem resistance among strains isolated from infected patients, carriers and hospital environment underlines the need for carbapenemase screening. Currently available methods vary in principle, accuracy and efficiency. The techniques that deserve particular attention belong to both easily accessible unsophisticated methods as well as advanced techniques based on mass spectrometry or molecular biology. While carbapenemases limit the therapeutic options in A. baumannii infections, studies concerning novel beta-lactamase inhibitors offer a new insight into effective therapy.

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“…A pilot study assessing A. baumannii infection of bone in a rat model has also been performed (45). Virulence factors that have been identified using this approach include penicillinbinding protein 7/8 (20), a glycosyltransferase (LpsB) involved in LPS biosynthesis (23), and genes (ptk and epsA) important for capsule formation (22). Phospholipase D was shown to be important for growth in human serum and for epithelial cell invasion, but in the murine pneumonia model, similar bacterial burdens and histopathology were identified (24).…”

Section: Use Of In Vivo Mammalian Model Systems To Study a Baumanniimentioning

confidence: 99%

Insights into Acinetobacter baumannii pathogenicity

2011

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SummaryAcinetobacter spp. have justifiably received significant attention from the public, scientific, and medical communities. Over recent years, Acinetobacter, particularly Acinetobacter baumannii, has become a ''red-alert'' human pathogen, primarily because of its exceptional ability to develop resistance to all currently available antibiotics. This characteristic is compounded by its unique abilities to survive in a diverse range of environments, including those within healthcare institutions, leading to problematic outbreaks. Historically, the virulence of the organism has been questioned, but recent clinical reports suggest that Acinetobacter can cause serious, life-threatening infections. Furthermore, its metabolic adaptability gives it a selective advantage in harsh hospital environments. This review focuses on current understanding of A. baumannii pathogenesis and the model systems used to study this interesting organism.

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Identification and Characterization of a Glycosyltransferase Involved in Acinetobacter baumannii Lipopolysaccharide Core Biosynthesis

Cited by 104 publications

References 44 publications

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation

RNA-Mediated cis Regulation in Acinetobacter baumannii Modulates Stress-Induced Phenotypic Variation

Acinetobacter baumannii: biology and drug resistance — role of carbapenemases

Insights into Acinetobacter baumannii pathogenicity

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