Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains

The increasing emergence of multidrug-resistant Acinetobacter baumannii constitutes a worldwide threat in hospital settings. Efflux-mediated resistance, particularly the resistancenodulation-division (RND)-type efflux pumps, contributes significantly to decreased susceptibility to multiple antibiotics when overexpressed. Using PCR-based detection, the prevalence of genes encoding the RND efflux pumps AdeB, AdeJ and AdeG was investigated amongst 144 epidemiologically characterized and geographically diverse A. baumannii isolates of worldwide origin, representing International Clones 1-8 and genotypically unique isolates. Furthermore, five putative RND-type efflux genes identified via an in silico approach were included. Five of the eight investigated efflux pump genes were present in all isolates, including adeJ and adeG; the prevalence of the others varied between 65 and 97 %. No association between the presence of one or multiple pumps to a specific clonal lineage was detected. The high prevalence of the efflux pump genes supports a fixed function of each individual pump that is not yet fully understood.

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“…Previously, Nemec et al (2007) found that 82% of A. baumannii isolates from a predominantly European collection carried adeB.…”

Section: Discussionmentioning

confidence: 99%

“…Nemec et al (2007) reported that the adeB gene was present in 87% of 116 genetically diverse predominantly European A. baumannii isolates. Other studies dealt with genetically related isolates (Huys et al, 2005b) or worked with a collection from one particular hospital (Chu et al, 2006;Lin et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of eight resistance-nodulation-division efflux pump genes in epidemiologically characterized Acinetobacter baumannii of worldwide origin

Nowak

Seifert

Higgins

2015

Journal of Medical Microbiology

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Section: Genes Of Adeabc System and Functionmentioning

confidence: 99%

“…However, the genes encoded RND efflux pumps are mainly located on the chromosome, they are detected with the different frequency [19,41,82]. The gene of the main AdeB transporter was detected by Chu et al [19] with the frequency of the 70% whether the 87% through Nemec et al [82]. All both structural and two-component regulatory system genes were stated about 40% of examined strains, in the remaining cases all sorts combinations of the presence of these genes were being watched [82].…”

Section: Genes Of Adeabc System and Functionmentioning

confidence: 99%

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

Wieczorek

Sacha²,

Hauschild³

et al. 2008

Folia Histochem Cytobiol.

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Abstract:Acinetobacter baumannii is an opportunistic pathogen which play the more and more greater role in the pathogenicity of the human. It is often attached with the hospital environment, in which is able easily to survive for many days even in adverse conditions. Acinetobacter baumannii is the species responsible for a serious nosocomial infections, especially in the intensive care units. Option of surviving in natural niches, and in the hospital environment could also be associated with the efflux pump mechanisms. Mechanisms of efflux universally appear in all cells (eukaryotic and prokaryotic) and play the physiological important role. In prokaryote, the main functions are evasion of such naturally produced molecules, removal of metabolic products and toxins. These pumps could also be involved in an early stage of infection, such as adhesion to host cells and the colonization. Importantly, they remove commonly used antibiotics from the cell in therapy of infections caused by these bacteria. Efflux pumps exemplify a unique phenomenon in drug resistance: a single mechanism causing resistance against several different classes of antibiotics. In Acinetobacter baumannii, the AdeABC efflux pump, a member of the resistance-nodulation-cell division family (RND), has been well characterized. Aminoglicosides, tetracyclines, erythromycin, chloramphenicol, trimethoprim, fluoroquinolones, some β-lactams, and also recently tigecycline, were found to be substrates for this pump. Drugs, as substrates for the AdeABC pump, can increase the expression of the AdeABC genes, leading to multidrug resistance (MDR). From this reason, treatment failure and death caused by Acinetobacter baumannii infections or underlying diseases are common. Because the AdeABC pump is widespread in Acinetobacter baumannii, similarly to other pumps in Gram-negative and Gram-positive bacteria, exists a need of searching a new therapeutic solutions. Specific efflux inhibitors of pumps (EPIs), including AdeABC inhibitors, could be suppress the activity of pumps and restore the sensitivity of such important bacteria as Acinetobacter baumannii to commonly used antibiotic.

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“…Many clinical A. baumannii isolates harbour different genetic arrangements of the adeRS and adeABC operons 39 . Examination into one A. baumannii clinical isolate identified that insertionalinactivation of the outer membrane component of the pump (AdeC) did not affect resistance towards two previously identified AdeABC substrates 25 .…”

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confidence: 99%

A key regulatory mechanism of antimicrobial resistance in pathogenic Acinetobacter baumannii

Adams¹

2017

Microbiol. Aust.

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Acinetobacter baumannii is a Gram-negative bacterial pathogen that has become a pressing global health issue in recent decades. Although virulence factors for this pathogen have been identified, details of how they are regulated are largely unknown. One widely employed regulatory mechanism that bacteria, such as A. baumannii, have adopted is through two component signal transduction systems (TCS). TCS consist of two proteins; a histidine kinase and response regulator. The histidine kinase allows the bacterium to sense alterations in the extracellular milieu, transmitting the information to the response regulator which prompts the cell to modify gene expression levels accordingly. Bacteria can encode multiple TCS, where each system can mediate specific responses to particular conditions or stressors. Identifying those conditions in which these TCS are expressed, and the genes they regulate known as their ‘regulon', is vital for understanding how A. baumannii survives and persists within the hospital environment or the human host during infection. As we enter the post-antibiotic era, knowledge of TCS could prove to be invaluable, as they offer an alternative target for the treatment of multidrug resistant bacterial infections.

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Relationship between the AdeABC efflux system gene content, netilmicin susceptibility and multidrug resistance in a genotypically diverse collection of Acinetobacter baumannii strains

Abstract: The AdeABC genes are common in A. baumannii, but may be absent in some, mostly fully susceptible strains. Decreased susceptibility to netilmicin (MIC 4-32 mg/L) is associated with both the presence of these genes and multidrug resistance and may be indicative of AdeABC overexpression.

Cited by 77 publications

References 18 publications

Prevalence of eight resistance-nodulation-division efflux pump genes in epidemiologically characterized Acinetobacter baumannii of worldwide origin

Prevalence of eight resistance-nodulation-division efflux pump genes in epidemiologically characterized Acinetobacter baumannii of worldwide origin

Multidrug resistant Acinetobacter baumannii--the role of AdeABC (RND family) efflux pump in resistance to antibiotics.

A key regulatory mechanism of antimicrobial resistance in pathogenic Acinetobacter baumannii

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