Fosfomycin resistance in<i>Acinetobacter baumannii</i>is mediated by efflux through a major facilitator superfamily (MFS) transporter—AbaF

Sharma, Atin; Sharma, Rajnikant; Bhattacharyya, Tapas; Bhando, Timsy; Pathania, Ranjana

doi:10.1093/jac/dkw382

Cited by 86 publications

(80 citation statements)

References 29 publications

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“…The novel efflux pump AmvA mediates resistance to different classes of antibiotics, disinfectants, detergents, and dyes, such as erythromycin, acriflavine, benzalkonium chloride, and methyl viologen (Rajamohan et al, 2010). AbaF was recently identified as a novel efflux pump associated with fosfomycin resistance (Sharma et al, 2016). …”

Section: Antimicrobial Resistance Of a Baumanniimentioning

confidence: 99%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

706

585

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Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

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Section: Antimicrobial Resistance Of a Baumanniimentioning

confidence: 99%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

706

585

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“…The major facilitator efflux pump superfamily is represented by TetA [193], TetB [194], and CmlA [195], CraA [196] (responsible for tetracycline and chloramphenicol resistances, respectively), AmvA (mediating resistance towards different classes of molecules of antibacterial activity, such as disinfectants, detergents, and dyes, furthermore erythromycin, acriflavine, benzalkonium chloride, and methylviologen) [197], and finally, AbaF (responsible for fosfomycin resistance) [198].…”

Section: Efflux Pumpsmentioning

confidence: 99%

An Overview of Multi-Antibiotic Resistance in Pathogenic Bacteria - From Selected Genetic and Evolutionary Aspects - A Review

Fodor¹,

Ba²,

Deák³

et al. 2018

Preprint

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The challenge posed by multi-drug resistance (MDR) of pathogenic organisms, spectacularly manifested in the 6 “ESKAPE” bacterium (two Gram-positive, four Gram-negative) species, should invoke new comprehensive strategies, and needs cooperation of scientists with medical, veterinary and natural science background. This review is aimed at informing newcomers, coming from the field of biology and genetics, about problems related to rapidly emerging, new multi-drug resistant, pathogenic, bacteria. Unlike persistence, the antibiotic resistance is inherited. A functioning “resistance gene” makes a susceptible organism resistant to a given antibiotic, encoding for polypeptides capable of acting either as decomposing enzymes, or acting as trans-membrane pumps, or membrane structure components capable of modifying the permeability implementing a «by pass» mechanism enabling the antibiotic molecule to reach its cellular target(s). A functioning “sensitivity gene” encode for a polypeptide, capable (directly or indirectly) of transferring toxic molecules into target cells, or of metabolizing non-transferable to transferable, or non-toxic molecules to toxic derivatives. A gene of a normal function could act as a “sensitivity” gene in the presence of antibiotics of chemical structures similar to the natural substrate of the gene product, (enzyme or binding/ trans-membrane protein). The Agrocin 84 story is a good example. Multi-drug resistance is a phenotypic consequence of the sequential accumulation of mutations, and/or up-take of plasmids or genomic islands carrying resistance genes from the environment via horizontal gene transfer, mediated by conjugative plasmid or bacteriophage carrying mobile genetic elements. Both multi-drug resistance and collateral sensitivity are evolutionary products. Some revealed evolutionary process and their Lamarckian and Darwinian interpretations are discussed. Toolkits of comparative full-genome sequencing, genomics, experimental evolution and population genetics may provide perspectives for overcoming the invincibility of multi-drug panresistance. The status of some recently emerging pathogenic bacterium species with zoonic features and of veterinary background is also discussed.

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“…Additional evidence implicating efflux pumps in the pathogenicity of A. baumannii, and therefore its virulence has been observed in several studies. For instance, overexpression of the RND efflux pump AdeABC increased bacterial virulence in a murine model (12), while inactivation of the MFS efflux pump AbaF lowered bacterial virulence in a Caenorhabditis elegans model (13). However, to our knowledge, whether transporters belonging to the other efflux pump superfamilies participate in the motility and virulence of A. baumannii has yet to be determined.…”

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confidence: 99%

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

Pérez-Varela

Corral

Aranda

et al. 2019

Antimicrob Agents Chemother

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Although the relationship between Acinetobacter baumannii efflux pumps and antimicrobial resistance is well documented, less is known about the involvement of these proteins in the pathogenicity of this nosocomial pathogen. In previous work, we identified the AbaQ major facilitator superfamily (MFS) efflux pump and demonstrated its participation in the motility and virulence of A. baumannii. In the present study, we examined the role in these processes of A. baumannii transporters belonging to different superfamilies of efflux pumps. Genes encoding known or putative permeases belonging to efflux pump superfamilies other than the MFS were selected, and the corresponding knockouts were constructed. The antimicrobial susceptibilities of these mutants were consistent with previously reported data. In mutants of A. baumannii strain ATCC 17978 carrying inactivated genes encoding the efflux pumps A1S_2736 (resistance nodulation division [RND]), A1S_3371 (multidrug and toxic compound extrusion [MATE]), and A1S_0710 (small multidrug resistance [SMR]), as well as the newly described ATP-binding cassette (ABC) permeases A1S_1242 and A1S_2622, both surface-associated motility and virulence were reduced compared to the parental strain. However, inactivation of the genes encoding the known ABC permeases A1S_0536 and A1S_1535, the newly identified putative ABC permeases A1S_0027 and A1S_1057, or the proteobacterial antimicrobial compound efflux (PACE) transporters A1S_1503 and A1S_2063 had no effects on bacterial motility or virulence. Our results demonstrate the involvement of antimicrobial transporters belonging at least to five of the six known efflux pump superfamilies in both surface-associated motility and virulence in A. baumannii ATCC 17978.

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Fosfomycin resistance inAcinetobacter baumanniiis mediated by efflux through a major facilitator superfamily (MFS) transporter—AbaF

Abstract: The results of this study suggest that efflux is an important mechanism of fosfomycin resistance and AbaF is involved in fosfomycin resistance in A. baumannii. AbaF also seems to play a role in biofilm formation and virulence of A. baumannii.

Cited by 86 publications

References 29 publications

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

An Overview of Multi-Antibiotic Resistance in Pathogenic Bacteria - From Selected Genetic and Evolutionary Aspects - A Review

Roles of Efflux Pumps from Different Superfamilies in the Surface-Associated Motility and Virulence of Acinetobacter baumannii ATCC 17978

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