scholarly journals Role of OmpA in the Multidrug Resistance Phenotype of Acinetobacter baumannii

2013 ◽  
Vol 58 (3) ◽  
pp. 1806-1808 ◽  
Author(s):  
Younes Smani ◽  
Anna Fàbrega ◽  
Ignasi Roca ◽  
Viviana Sánchez-Encinales ◽  
Jordi Vila ◽  
...  

ABSTRACTAcinetobacter baumanniihas emerged as a nosocomial pathogen with an increased prevalence of multidrug-resistant strains. The role of the outer membrane protein A (OmpA) in antimicrobial resistance remains poorly understood. In this report, disruption of theompAgene led to decreased MICs of chloramphenicol, aztreonam, and nalidixic acid. We have characterized, for the first time, the contribution of OmpA in the antimicrobial resistance phenotype ofA. baumannii.

2013 ◽  
Vol 81 (7) ◽  
pp. 2574-2583 ◽  
Author(s):  
Bart A. Eijkelkamp ◽  
Uwe H. Stroeher ◽  
Karl A. Hassan ◽  
Liam D. H. Elbourne ◽  
Ian T. Paulsen ◽  
...  

ABSTRACTAcinetobacter baumanniihas become a major problem in the clinical setting with the prevalence of infections caused by multidrug-resistant strains on the increase. Nevertheless, only a limited number of molecular mechanisms involved in the success ofA. baumanniias a human pathogen have been described. In this study, we examined the virulence features of a hypermotile derivative ofA. baumanniistrain ATCC 17978, which was found to display enhanced adherence to human pneumocytes and elevated levels of lethality towardCaenorhabditis elegansnematodes. Analysis of cellular lipids revealed modifications to the fatty acid composition, providing a possible explanation for the observed changes in hydrophobicity and subsequent alteration in adherence and motility. Comparison of the genome sequences of the hypermotile variant and parental strain revealed that an insertion sequence had disrupted anhns-like gene in the variant. This gene encodes a homologue of the histone-like nucleoid structuring (H-NS) protein, a known global transcriptional repressor. Transcriptome analysis identified the global effects of this mutation on gene expression, with major changes seen in the autotransporter Ata, a type VI secretion system, and a type I pilus cluster. Interestingly, isolation and analysis of a second independent hypermotile ATCC 17978 variant revealed a mutation to a residue within the DNA binding region of H-NS. Taken together, these mutants indicate that the phenotypic and transcriptomic differences seen are due to loss of regulatory control effected by H-NS.


2007 ◽  
Vol 56 (12) ◽  
pp. 1595-1599 ◽  
Author(s):  
Justin Edwards ◽  
Geeta Patel ◽  
David W. Wareham

Acinetobacter baumannii is increasingly recognized as an important multidrug-resistant nosocomial pathogen. Recent work has highlighted enhanced growth and heightened virulence in the presence of ethyl alcohols. As alcohol-based hand rubs (ABHRs) are extensively used in health care settings, the authors set out to determine whether the hand rubs could also influence the growth of prevalent multidrug-resistant strains circulating in UK hospitals. A significant increase in growth was observed when minimal media were supplemented with concentrations of 1 % and lower of four commercially available hand rubs. In addition, growth in ABHR-supplemented media resulted in secretion of proteins into the culture supernatant. One of these was identified as OmpA, which is recognized as having emulsifying activity, which could potentially confer enhanced pathogenicity to A. baumannii.


2020 ◽  
Vol 202 (12) ◽  
Author(s):  
María Pérez-Varela ◽  
Aimee R. P. Tierney ◽  
Ju-Sim Kim ◽  
Andrés Vázquez-Torres ◽  
Philip Rather

ABSTRACT In response to nutrient depletion, the RelA and SpoT proteins generate the signaling molecule (p)ppGpp, which then controls a number of downstream effectors to modulate cell physiology. In Acinetobacter baumannii strain AB5075, a relA ortholog (ABUW_3302) was identified by a transposon insertion that conferred an unusual colony phenotype. An in-frame deletion in relA (ΔrelA) failed to produce detectable levels of ppGpp when amino acid starvation was induced with serine hydroxamate. The ΔrelA mutant was blocked from switching from the virulent opaque colony variant (VIR-O) to the avirulent translucent colony variant (AV-T), but the rate of AV-T to VIR-O switching was unchanged. In addition, the ΔrelA mutation resulted in a pronounced hypermotile phenotype on 0.35% agar plates. This hypermotility was dependent on the activation of a LysR regulator ABUW_1132, which was required for expression of AbaR, a LuxR family quorum-sensing regulator. In the ΔrelA mutant, ABUW_1132 was also required for the increased expression of an operon composed of the ABUW_3766-ABUW_3773 genes required for production of the surfactant-like lipopeptide acinetin 505. Additional phenotypes identified in the ΔrelA mutant included (i) cell elongation at high density, (ii) reduced formation of persister cells tolerant to colistin and rifampin, and (iii) decreased virulence in a Galleria mellonella model. IMPORTANCE Acinetobacter baumannii is a pathogen of worldwide importance. Due to the increasing prevalence of antibiotic resistance, these infections are becoming increasingly difficult to treat. New therapies are required to combat multidrug-resistant isolates. The role of RelA in A. baumannii is largely unknown. This study demonstrates that like in other bacteria, RelA controls a variety of functions, including virulence. Strategies to inhibit the activity of RelA and the resulting production of ppGpp could inhibit virulence and may represent a new therapeutic approach.


2018 ◽  
Vol 62 (9) ◽  
Author(s):  
María Pérez-Varela ◽  
Jordi Corral ◽  
Jesús Aranda ◽  
Jordi Barbé

ABSTRACTAcinetobacter baumanniihas emerged as an important multidrug-resistant nosocomial pathogen. In previous work, we identified a putative MFS transporter, AU097_RS17040, involved in the pathogenicity ofA. baumannii(M. Pérez-Varela, J. Corral, J. A. Vallejo, S. Rumbo-Feal, G. Bou, J. Aranda, and J. Barbé, Infect Immun 85:e00327-17, 2017,https://doi.org/10.1128/IAI.00327-17). In this study, we analyzed the susceptibility to diverse antimicrobial agents ofA. baumanniicells defective in this transporter, referred to as AbaQ. Our results showed that AbaQ is mainly involved in the extrusion of quinolone-type drugs inA. baumannii.


2018 ◽  
Vol 7 (5) ◽  
Author(s):  
Clay S. Crippen ◽  
Steven Huynh ◽  
William G. Miller ◽  
Craig T. Parker ◽  
Christine M. Szymanski

Antimicrobial resistance is a major problem worldwide. Understanding the interplay between drug-resistant pathogens, such as Acinetobacter baumannii and related species, potentially acting as environmental reservoirs is critical for preventing the spread of resistance determinants.


Author(s):  
Josephine Joy Hubloher ◽  
Kim Schabacker ◽  
Volker Müller ◽  
Beate Averhoff

The opportunistic human pathogen Acinetobacter baumannii has become one of the leading causes of nosocomial infections around the world due to the increasing prevalence of multidrug-resistant strains and their optimal adaptation to clinical environments and the human host. Recently, it was found that CsrA, a global mRNA binding posttranscriptional regulator, plays a role in osmotic stress adaptation, virulence, and growth on amino acids of A. baumannii AB09-003 and 17961.


2019 ◽  
Vol 8 (31) ◽  
Author(s):  
Nicholas Agyepong ◽  
Usha Govinden ◽  
Alex Owusu-Ofori ◽  
Mushal Allam ◽  
Arshad Ismail ◽  
...  

Multidrug-resistant Acinetobacter baumannii is a major nosocomial pathogen. We describe the whole-genome sequences of two multidrug-resistant Acinetobacter baumannii strains isolated from hospitalized patients in the intensive care unit at Komfo Anokye Teaching Hospital in Ghana. The isolates carry multiple resistance genes, including those for β-lactams, sulfonamides, aminoglycosides, and tetracycline.


2003 ◽  
Vol 24 (4) ◽  
pp. 275-279 ◽  
Author(s):  
Cosmina Zeana ◽  
Elaine Larson ◽  
Jyoti Sahni ◽  
S. J. Bayuga ◽  
Fann Wu ◽  
...  

AbstractObjective:To explore the role of the community as a potential reservoir forAcinetobacter baumannii.Design:Antimicrobial resistance patterns and genotypes ofA. baumanniiisolates from patients in two Manhattan hospitals were compared with those ofA. baumanniiisolates from the hands of community members.Results:A total of 103 isolates from two hospitals (hospital A, 81; hospital B, 22) and 23 isolates from community residents were studied. Of the hospital isolates, 36.6% were multidrug resistant (hospital A, 68.2%; hospital B, 27.8%). In contrast, there were no multidrug-resistant isolates from the community (P< .005 between hospital and community). The prevalence ofA. baumanniion the hands of community residents was 10.4% (23 of 222). By molecular typing, 42 strains of A.baumanniiwere identified. Of the isolates from hospital A and hospital B, 55.6% (45 of 81) and 68.2% (15 of 22), respectively, were indistinguishable or closely related. In contrast, most community (83.3%) isolates were unrelated (P= .001 between hospital and community).Conclusion:Acinetobacterisolates from the community, characterized by a large variety of unrelated strains (83.3%), were distinct from the hospital isolates, of which 58.3% were closely related. The absence of multidrug-resistant strains in the community compared with 36.6% prevalence among hospital isolates suggests that the reservoir for epidemic strains resides in the hospital environment itself. To our knowledge, this is the first study to examine the community as a potential reservoir for hospital strains ofA. baumannii.


2017 ◽  
Vol 55 (6) ◽  
pp. 1920-1927 ◽  
Author(s):  
Jim Werngren ◽  
Erik Alm ◽  
Mikael Mansjö

ABSTRACTPyrazinamide (PZA) is a key component for the effective treatment of drug-susceptible and PZA-susceptible multidrug-resistant (MDRPZA-S) tuberculosis (TB).pncAgene mutations are usually detected in a clear majority (>90%) of PZA-resistant strains but obviously not in all. Rapid and reliable PZA drug susceptibility testing (DST) is critical whenever PZA is to be used in a treatment regimen, not least for the treatment of MDRPZA-STB. In this study, we selected 26 PZA-resistant isolates reported to carry a wild-typepncAgene. To confirm resistance, susceptibility testing was repeated using 100 mg/liter and 200 mg/liter PZA for all the 26 isolates and Sanger sequencing was repeated on the 18 isolates that remained PZA resistant. Apart from the eight isolates initially misclassified as PZA resistant, the retests identified three factors responsible for the phenotype-genotype discrepancy:panDorrpsAmutations identified by whole-genome sequencing (WGS) (n= 7), heteroresistance (n= 8), and mixed populations withMycobacterium avium(n= 3). Additionally, we performed WGS on 400 PZA-susceptible isolates and 15 consecutive MDRPZA-Rclinical isolates. Of the 400 PZA-susceptible isolates, only 1 harbored a nonsynonymouspncAmutation (Thr87Met), whereas a nonsynonymousrpsAmutation was found in 17 isolates. None of these isolates carried a nonsynonymouspanDmutation, while all 15 of the MDRPZA-Risolates harbored a nonsynonymouspncAmutation. Our findings indicate that it is necessary to consider the occurrence ofpanDmutations in PZA-resistant isolates, as well as heteroresistance, for the development and evaluation of new molecular techniques to ensure high-quality DST performance. The identification of nonsynonymousrpsAmutations in both PZA-susceptible and PZA-resistant isolates also implies that further studies are needed in order to determine the role ofrpsAin PZA resistance.


2014 ◽  
Vol 82 (9) ◽  
pp. 3910-3918 ◽  
Author(s):  
Patrick M. Ketter ◽  
M. Neal Guentzel ◽  
Beverly Schaffer ◽  
Maryanne Herzig ◽  
Xiaowu Wu ◽  
...  

ABSTRACTMultidrug-resistantAcinetobacter baumanniiis among the most prevalent bacterial pathogens associated with trauma-related wound and bloodstream infections. Although septic shock and disseminated intravascular coagulation have been reported following fulminantA. baumanniisepsis, little is known about the protective host immune response to this pathogen. In this study, we examined the role of PTX3, a soluble pattern recognition receptor with reported antimicrobial properties and stored within neutrophil granules. PTX3 production by murine J774a.1 macrophages was assessed following challenge withA. baumanniistrains ATCC 19606 and clinical isolates (CI) 77, 78, 79, 80, and 86. Interestingly, only CI strains 79, 80, and 86 induced PTX3 synthesis in murine J774a.1 macrophages, with greatest production observed following CI 79 and 86 challenge. Subsequently, C57BL/6 mice were challenged intraperitoneally with CI 77 and 79 to assess the role of PTX3in vivo.A. baumanniistrain CI 79 exhibited significantly (P< 0.0005) increased mortality, with an approximate 50% lethal dose (LD50) of 105CFU, while an equivalent dose of CI 77 exhibited no mortality. Plasma leukocyte chemokines (KC, MCP-1, and RANTES) and myeloperoxidase activity were also significantly elevated following challenge with CI 79, indicating neutrophil recruitment/activation associated with significant elevation in serum PTX3 levels. Furthermore, 10-fold-greater PTX3 levels were observed in mouse serum 12 h postchallenge, comparing CI 79 to CI 77 (1,561 ng/ml versus 145 ng/ml), with concomitant severe pathology (liver and spleen) and coagulopathy. Together, these results suggest that elevation of PTX3 is associated with fulminant disease duringA. baumanniisepsis.


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