Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy

Giannouli, Maria; Popolo, Anna Di; Durante‐Mangoni, Emanuele; Bernardo, Mariano; Cuccurullo, Susanna; Amato, Gerardino; Tripodi, Marie‐Francoise; Triassi, Maria; Utili, Riccardo; Zarrilli, Raffaele

doi:10.1016/j.ijantimicag.2011.09.016

Cited by 50 publications

(45 citation statements)

References 20 publications

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“…These base-pair substitutions can be the result of error-prone DNA polymerase, such as DNA Pol V (39). A. baumannii clinical Rif r isolates have been shown to have mutations in rpoB (54), validating this assay for use in A. baumannii. Both parental strain A. baumannii ATCC 17978 and the recA::Km isogenic strains were tested for induced mutagenesis by selecting for Rif r mutants after exposure to UV and to the alkylating agent MMS.…”

Section: Resultsmentioning

confidence: 77%

“…be acquired through the recA-dependent DNA damage response in A. baumannii, likely resulting from DNA base-pair substitutions in the rpoB gene (54). The data for the dinB::Km strain also suggest a role for A. baumannii DinB in generating spontaneous mutations and emphasize that the multiple DNA Pol V enzymes likely have a greater role in induced mutagenesis.…”

Section: Resultsmentioning

confidence: 85%

“…We set forth to test whether the A. baumannii recA-dependent DNA damage response is responsible for DNA damage-induced mutagenesis by using an established Rif r assay (65). Rifampin is an antibiotic frequently coupled with colistin and used by clinicians to treat multidrug-resistant A. baumannii infections (54). Rifampin targets the ␤ subunit of the bacterial RNA polymerase holoenzyme, RpoB.…”

Section: Resultsmentioning

confidence: 99%

“…Colony PCR was performed according to the GoTaq 2ϫ master mix (Promega) protocol on 32 individual desiccation-induced Rif r mutants from 6 independent A. baumannii ATCC 17978 recA ϩ experiments and also on 10 individual dinB::Km Rif r mutants from 5 independent A. baumannii ATCC 17978 dinB::Km experiments. Oligonucleotides rpoB-1441F and rpoB-2095R (Table 1) amplify a 654-bp region of rpoB (locus A1S_0287) where Rif r -inducing base-pair substitutions are frequently located (54). Sequencing (Tufts Core Facility) was carried out using the same oligonucleotide set.…”

Section: Methodsmentioning

confidence: 99%

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Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Norton

Spilkia

Godoy

2013

Journal of Bacteriology

112

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Acinetobacter baumannii is an emerging nosocomial, opportunistic pathogen that survives desiccation and quickly acquires resistance to multiple antibiotics. Escherichia coli gains antibiotic resistances by expressing genes involved in a global response to DNA damage. Therefore, we asked whether A. baumannii does the same through a yet undetermined DNA damage response akin to the E. coli paradigm. We found that recA and all of the multiple error-prone DNA polymerase V (Pol V) genes, those organized as umuDC operons and unlinked, are induced upon DNA damage in a RecA-mediated fashion. Consequently, we found that the frequency of rifampin-resistant (Rif r ) mutants is dramatically increased upon UV treatment, alkylation damage, and desiccation, also in a RecA-mediated manner. However, in the recA insertion knockout strain, in which we could measure the recA transcript, we found that recA was induced by DNA damage, while uvrA and one of the unlinked umuC genes were somewhat derepressed in the absence of DNA damage. Thus, the mechanism regulating the A. baumannii DNA damage response is likely different from that in E. coli. Notably, it appears that the number of DNA Pol V genes may directly contribute to desiccation-induced mutagenesis. Sequences of the rpoB gene from desiccation-induced Rif r mutants showed a signature that was consistent with E. coli DNA polymerase V-generated base-pair substitutions and that matched that of sequenced A. baumannii clinical Rif r isolates. These data strongly support an A. baumannii DNA damage-inducible response that directly contributes to antibiotic resistance acquisition, particularly in hospitals where A. baumannii desiccates and tenaciously survives on equipment and surfaces.

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Section: Resultsmentioning

confidence: 77%

Section: Resultsmentioning

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Norton

Spilkia

Godoy

2013

Journal of Bacteriology

112

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“…Other antibiotics which combine with rifampicin may be related to substantial changes in the outer membrane of A. baumannii isolates; thus enhancing the ability of rifampicin to penetrate into the cell 29 . The effectiveness of rifampicin in antimicrobial combinations, however, could depend on the degree of sensitivity and specific resistance mechanisms of individual A. baumannii isolates 30 .…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

Tunyapanit¹,

Pruekprasert²,

Laoprasopwattana³

et al. 2014

ScienceAsia

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ABSTRACT:The incidence of multidrug-resistant Acinetobacter baumannii (MDR A. baumannii) is increasing worldwide and is leading to therapeutic problems. We investigated the in vitro activities of cefoperazone/sulbactam, colistin, imipenem, and rifampicin alone and in double combinations against 100 A. baumannii isolates from patients at Songklanagarind Hospital in Songkhla Province, Thailand. The E-test method was used to determine antimicrobial susceptibility, the minimal inhibitory concentration (MIC) and for antimicrobial combination testing. A. baumannii isolates were susceptible to colistin (97%), cefoperazone/sulbactam (69%), imipenem (45%), and rifampicin (13%). Fifty-nine percent of them were MDR A. baumannii. Colistin was superior to cefoperazone/sulbactam, rifampicin and imipenem against MDR A. baumannii and the MIC50, MIC90 of colistin were 0.75 and 1 µg/ml, respectively. Non-MDR A. baumannii isolates were susceptible to cefoperazone/sulbactam (100%), colistin (95%), imipenem (93%) and rifampicin (2%). Combinations of cefoperazone/sulbactam plus colistin or rifampicin, imipenem plus colistin or rifampicin and colistin plus rifampicin showed indifferent effects against most MDR isolates. Of all the antimicrobial combinations tested, cefoperazone/sulbactam plus rifampicin produced the highest percentages (42%) of synergy, partial synergy, and additive results. The activity rate of cefoperazone/sulbactam against MDR A. baumannii was higher when combined with rifampicin than colistin. Thus colistin had the greatest activity against most MDR and non-MDR A. baumannii isolates among all of the antibiotics tested. Cefoperazone/sulbactam and imipenem showed good activity against non-MDR isolates, and cefoperazone/sulbactam combined with rifampicin may be useful in treating infections caused by MDR isolates.

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A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics

et al. 2020

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In order to mitigate antibiotic resistance, a new strategy to increase antibiotic potency and reverse drug resistance is needed. Herein, the translocation mechanism of an antimicrobial guanidinium‐functionalized polycarbonate is leveraged in combination with traditional antibiotics to afford a potent treatment for drug‐resistant bacteria. Particularly, this polymer–antibiotic combination approach reverses rifampicin resistance phenotype in Acinetobacter baumannii demonstrating a 2.5 × 105‐fold reduction in minimum inhibitory concentration (MIC) and a 4096‐fold reduction in minimum bactericidal concentration (MBC). This approach also enables the repurposing of auranofin as an antibiotic against multidrug‐resistant (MDR) Gram‐negative bacteria with a 512‐fold MIC and 128‐fold MBC reduction, respectively. Finally, the in vivo efficacy of polymer–rifampicin combination is demonstrated in a MDR bacteremia mouse model. This combination approach lays foundational ground rules for a new class of antibiotic adjuvants capable of reversing drug resistance phenotype and repurposing drugs against MDR Gram‐negative bacteria.

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Molecular epidemiology and mechanisms of rifampicin resistance in Acinetobacter baumannii isolates from Italy

Cited by 50 publications

References 20 publications

Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Antibiotic Resistance Acquired through a DNA Damage-Inducible Response in Acinetobacter baumannii

Antimicrobial susceptibility of Acinetobacter baumannii isolated from hospital patients

A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics

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