Competence for Natural Transformation Is Common among Clinical Strains of Resistant Acinetobacter spp.

Domingues, Sara; Rosário, Natasha; Cândido, Ângela; Neto, Daniela; Nielsen, Kaare M.; Silva, Gabriela

doi:10.3390/microorganisms7020030

Cited by 42 publications

(35 citation statements)

References 21 publications

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“… A. baumannii and related species A. nosocomialis were described as transformable in 2013 ( 13 , 14 ). In A. baumannii , natural transformation appears as a conserved trait among clinical and nonclinical isolates of human and animal origin ( 13 , 15 , 16 ), providing the bacteria with a major route for acquisition of antibiotic resistance genes.…”

Section: Introductionmentioning

confidence: 99%

Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii

Godeux

Svedholm

Lupo

et al. 2020

Antimicrob Agents Chemother

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With a great diversity in gene composition including multiple putative antibiotic-resistance genes, AbaR islands are potential contributors to multi-drug resistance in Acinetobacter baumannii. However, the effective contribution of AbaR to antibiotic resistance and bacterial physiology remains elusive. To address this, we sought to accurately remove AbaR islands and restore the integrity of their insertion site. To this end, we devised a versatile scarless genome editing strategy. We performed this genetic modification in two recent A. baumannii clinical strains: the strain AB5075 and the nosocomial strain AYE which carry AbaR11 and AbaR1 islands of 19.7 kbp and 86.2 kbp, respectively. Antibiotic susceptibilities were then compared between the parental strains and their AbaR-cured derivatives. As anticipated by the predicted function of the ORF of this island, the antibiotic resistance profiles were identical between the wild type and the AbaR11-cured AB5075 strains. In contrast, AbaR1 carries 25 ORFs with a predicted resistance to several classes of antibiotics and the AYE AbaR1-cured derivative showed restored susceptibility to multiple classes of antibiotics. Moreover, curing of AbaRs restored high levels of natural transformability. Indeed, most AbaR islands are inserted into the comM gene involved in natural transformation. Our data indicate that AbaR insertion effectively inactivates comM and that the restored comM is functional. Curing of AbaR consistently resulted in highly transformable, and therefore, easily genetically tractable strains. Emendation of AbaR provides insight into the functional consequences of AbaR acquisition.

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Section: Introductionmentioning

confidence: 99%

Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii

Godeux

Svedholm

Lupo

et al. 2020

Antimicrob Agents Chemother

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show abstract

“…To test our hypothesis, three model strains (A118, A42, and AB5075) with varying degrees of antibiotic susceptibility and virulence were used (Ramirez et al, 2010; Ramirez et al, 2011; Vilacoba et al, 2013; Jacobs et al, 2014; Traglia et al, 2016). A118, the least antibiotic-resistant and virulent strain, was selected to perform transcriptomic analysis, metabolic microarrays, and virulence testing as the strain has been previously used as a model system (Ramirez et al, 2010; Ramirez et al, 2012; Traglia et al, 2016; Domingues et al, 2018; Martinez et al, 2018; Quinn et al, 2018a,b,c; Domingues et al, 2019). A42, the mildly resistant and virulent strain, and AB5075, the most resistant and virulent, were then used to supplement our assessment of the A. baumannii metabolic profile in response to PF.…”

Section: Introductionmentioning

confidence: 99%

Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

et al. 2019

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Acinetobacter baumannii ( Ab ) is one of the most treacherous pathogens among those causing hospital-acquired pneumonia (HAP). A. baumannii possesses an adaptable physiology, seen not only in its antibiotic resistance and virulence phenotypes but also in its metabolic versatility. In this study, we observed that A. baumannii undergoes global transcriptional changes in response to human pleural fluid (PF), a key host-derived environmental signal. Differential gene expression analyses combined with experimental approaches revealed changes in A. baumannii metabolism, affecting cytotoxicity, persistence, bacterial killing, and chemotaxis. Over 1,220 genes representing 55% of the differentially expressed transcriptomic data corresponded to metabolic processes, including the upregulation of glutamate, short chain fatty acid, and styrene metabolism. We observed an upregulation by 1.83- and 2.61-fold of the pyruvate dehydrogenase complex subunits E3 and E2, respectively. We also found that pyruvate (PYR), in conjunction with PF, triggers an A. baumannii pathogenic behavior that adversely impacts human epithelial cell viability. Interestingly, PF also amplified A. baumannii cytotoxicity against murine macrophages, suggesting an immune evasion strategy implemented by A. baumannii . Moreover, we uncovered opposing metabolic strategies dependent on the degree of pathogenicity of the strains, where less pathogenic strains demonstrated greater utilization of PYR to promote persister formation in the presence of PF. Additionally, our transcriptomic analysis and growth studies of A. baumannii suggest the existence of an alternative phenylalanine (PA) catabolic route independent of the phenylacetic acid pathway, which converts PA to phenylpyruvate (PP) and shuttles intermediates into styrene metabolism. This alternative route promoted a neutrophil-evasive state, as PF-induced degradation of PP significantly reduced overall human neutrophil chemotaxis in ex vivo chemotactic assays. Taken together, these data highlight A. baumannii pathoadaptabililty in response to host signals and provide further insight into the role of bacterial metabolism in virulence traits, antibiotic persistence strategies, and host innate immune evasion.

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“…Acinetobacter spp. is naturally competent with high natural transformation rates that have an essential role in antibiotic resistance genes gaining and distribution [ 18 , 19 ]. For a long time, carbapenem was the best drug to control A. baumannii infections; however, the evolved carbapenem resistance due to carbapenemase limited its efficacy [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Antibiogram, Prevalence of OXA Carbapenemase Encoding Genes, and RAPD-Genotyping of Multidrug-Resistant Acinetobacter baumannii Incriminated in Hidden Community-Acquired Infections

et al. 2020

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Acinetobacter spp. has gained fame from their ability to resist difficult conditions and their constant development of antimicrobial resistance. This study aimed to investigate the prevalence, susceptibility testing, OXA carbapenemase-encoding genes, and RAPD-genotyping of multidrug resistant Acinetobacter baumannii incriminated in hidden community-acquired infections in Egypt. The antimicrobial susceptibility testing was assessed phenotypically using Kirby–Bauer disk diffusion method. Also, Modified-Hodge test (MHT) was carried out to detect the carbapenemases production. Multiplex-PCR was used to detect the carbapenemase-encoding genes. Furthermore, the genetic relationship among the isolated strains was investigated using RAPD fingerprinting. The bacteriological examination revealed that, out of 200 Gram-negative non-fermentative isolates, 44 (22%) were identified phenotypically and biochemically as Acinetobacter spp. and 23 (11.5%) were molecularly confirmed as A.baumannii. The retrieved A.baumannii strains were isolated from urine (69%), sputum (22%), and cerebrospinal fluid (csf) (9%). The isolated A. baumannii strains exhibited multidrug resistance and the production rates of carbapenemases were 56.5, 60.9, and 78.3% with meropenem, imipenem, and ertapenem disks, respectively. The blaOXA-24-like genes were the most predominant among the tested strains (65.2%), followed by blaOXA-23 (30.4%) and blaOXA-58 (17.4%), in addition, the examined strains are harbored IMP, VIM, and NDM genes with prevalence of 60.9, 43.5, and 13%, respectively, while KPC and GES genes were not detected. RAPD-PCR revealed that the examined strains are clustered into 11 different genotypes at ≥90% similarity. Briefly, to the best of our knowledge, this study is the first report concerning community-associated A. baumannii infections in Egypt. The high prevalence of hidden multidrug-resistant (MDR) and extensively drug-resistant (XDR) A.baumannii strains associated with non-hospitalized patients raises an alarm for healthcare authorities to set strict standards to control the spread of such pathogens with high rates of morbidity and mortality.

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Competence for Natural Transformation Is Common among Clinical Strains of Resistant Acinetobacter spp.

Cited by 42 publications

References 21 publications

Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii

Scarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumannii

Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

Antibiogram, Prevalence of OXA Carbapenemase Encoding Genes, and RAPD-Genotyping of Multidrug-Resistant Acinetobacter baumannii Incriminated in Hidden Community-Acquired Infections

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