Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii

Hood, M. Indriati; Becker, Kyle W.; Roux, Christelle M.; Dunman, Paul M.; Skaar, Eric P.

doi:10.1128/iai.00704-12

Cited by 59 publications

(59 citation statements)

References 39 publications

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“…Acinetobacter spp. have also been shown to acquire mutations in the lipid A biosynthetic pathway when treated with colistin, resulting in resistance to the antibiotic (40)(41)(42)(43). Interestingly, those studies found that mutations in certain lipid A genes resulted in complete loss of LOS.…”

Section: Cell Surfacementioning

confidence: 99%

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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Section: Cell Surfacementioning

confidence: 99%

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

2016

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“…All animal experiments were approved by the Vanderbilt University Institutional Animal Care and Use Committee. The murine model of A. baumannii pneumonia was performed as previously described (44)(45)(46)(47)(48)(49). Briefly, Ab17978 bacteria were back-diluted 1:1,000 from an overnight culture and grown for 3.5 h at 37°C with shaking, washed twice with cold phosphate-buffered saline (PBS), and resuspended in PBS at an appropriate cell density for infection.…”

Section: Methodsmentioning

confidence: 99%

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

et al. 2017

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The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor capable of recognizing multiple pathogen-associated and dangerassociated molecular patterns that contributes to the initiation and potentiation of inflammation in many disease processes. During infection, RAGE functions to either exacerbate disease severity or enhance pathogen clearance depending on the pathogen studied. Acinetobacter baumannii is an opportunistic human pathogen capable of causing severe infections, including pneumonia and sepsis, in impaired hosts. The role of RAGE signaling in response to opportunistic bacterial infections is largely unknown. In murine models of A. baumannii pneumonia, RAGE signaling alters neither inflammation nor bacterial clearance. In contrast, RAGE Ϫ/Ϫ mice systemically infected with A. baumannii exhibit increased survival and reduced bacterial burdens in the liver and spleen. The increased survival of RAGE Ϫ/Ϫ mice is associated with increased circulating levels of the anti-inflammatory cytokine interleukin-10 (IL-10). Neutralization of IL-10 in RAGE Ϫ/Ϫ mice results in decreased survival during systemic A. baumannii infection that mirrors that of wild-type (WT) mice, and exogenous IL-10 administration to WT mice enhances survival in this model. These findings demonstrate the role for RAGE-dependent IL-10 suppression as a key modulator of mortality from Gram-negative sepsis.KEYWORDS Acinetobacter baumannii, IL-10, innate immunity, pneumonia, RAGE, receptor for advanced glycation end products, sepsis A n effective immune response to an invading pathogen depends upon host recognition of the infecting organism and resultant initiation of an immune response. This process is accomplished through the recognition of pathogen-associated molecular patterns (PAMPs) by host pattern recognition receptors (PRRs) (1). Signaling downstream of PRRs, including Toll-like receptors (TLRs), activates transcription factors such as nuclear factor kappa B (NF-B), inducing expression of proinflammatory genes and thereby altering cytokine and chemokine production, resulting in inflammation and effector cell recruitment to the site of infection (1, 2). In addition to PAMPs, many PRRs have also evolved to detect altered host proteins, referred to as danger-associated molecular patterns (DAMPs) (3). The signaling mechanisms required to initiate an appropriate response to an invading pathogen may also potentiate inflammation during the course of infection, and this inflammatory response may enhance tissue damage and exacerbate disease (4). The maladaptive potentiation of inflammation in response to infection is responsible for many of the severe manifestations of infectious

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“…All animal experiments were approved by the Vanderbilt University Institutional Animal Care and Use Committee. The murine model of A. baumannii pneumonia was performed as previously described (31)(32)(33)(34)(35)(36). Briefly, A. baumannii ATCC 17978 bacteria were back diluted 1:1,000 from overnight culture and grown for 3.5 h at 37°C with shaking, washed twice with cold PBS, and resuspended in PBS at an appropriate cell density for infection.…”

Section: Methodsmentioning

confidence: 99%

Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection

et al. 2015

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dAcinetobacter baumannii is a common nosocomial pathogen capable of causing severe diseases associated with significant morbidity and mortality in impaired hosts. Pattern recognition receptors, such as the Toll-like receptors (TLRs), play a key role in pathogen detection and function to alert the immune system to infection. Here, we examine the role for TLR9 signaling in response to A. baumannii infection. In a murine model of A. baumannii pneumonia, TLR9؊/؊ mice exhibit significantly increased bacterial burdens in the lungs, increased extrapulmonary bacterial dissemination, and more severe lung pathology compared with those in wild-type mice. Following systemic A. baumannii infection, TLR9؊/؊ mice have significantly increased bacterial burdens in the lungs, as well as decreased proinflammatory cytokine and chemokine production. These results demonstrate that TLR9-mediated pathogen detection is important for host defense against the opportunistic pathogen Acinetobacter baumannii.

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Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii

Cited by 59 publications

References 39 publications

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

Pathogenic Acinetobacter: from the Cell Surface to Infinity and Beyond

RAGE-Mediated Suppression of Interleukin-10 Results in Enhanced Mortality in a Murine Model of Acinetobacter baumannii Sepsis

Toll-Like Receptor 9 Contributes to Defense against Acinetobacter baumannii Infection

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