The Journal of Practical Medicine >

2023 , Vol. 39 >Issue 16: 2122 - 2129

DOI: https://doi.org/10.3969/j.issn.1006-5725.2023.16.019

Medical Examination and Clinical Diagnosis

Analysis of efflux pump and outer membrane protein of multi⁃drug resistant Acinetobacter baumannii

  • Yubo HUANG ,
  • Yuqi ZHOU ,
  • Wenzheng ZHENG ,
  • Jiaxin ZHU ,
  • Hailing YANG ,
  • Wenbin WU ,
  • Tiantuo. ZHANG
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  • Department of Respiratory and Critical Medicine，the Third Affiliated Hospital of Sun Yat?sen University，Guangzhou 510630，China

Received date: 2023-07-14

  Online published: 2023-09-26

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Abstract

Objective To analyze the sensitivity of Acinetobacter baumannii （A. baumannii） to common antibiotics， and to detect the expression level of efflux pump genes and outer membrane protein （OMP） genes and to explore the relationship between the expression of these genes and antibiotic resistance. Methods A total of 213 isolates of multidrug?resistant A. baumannii from the lower respiratory tract of inpatients from our hospital were collected. Susceptibility testing was conducted by K?B disk diffusion method. According to the drug sensitivity test， they were divided into non?sensitive groups （NS groups） and sensitive groups （S groups）. The expression level of efflux pump genes （adeB， adeJ， adeG， craA， abeM， amvA） and OMP genes （omp25， omp33?36， carO） were detected by fluorescence quantitative PCR， and the differences of these genes between NS groups and S groups were compared. Results The insensitive rates of A. baumannii to amikacin and imipenem were 89.2% and 81.2% respectively， and the insensitive rates to piperacillin/tazobactam， cefoperazone/ sulbactam and gentamicin were more than 92%. The distribution of increased relative expression of adeB gene （RE≥1） in NS and S groups of antibiotics （AMK， IPM， CFP， FEP， TZP， CAZ， SXT， CIP， SCF， CN） was analyzed respectively. The results showed that the proportion of RE ≥ 1 in most antibiotic NS groups was significantly higher than that in S groups， suggesting that the overexpression of adeB was closely related to the above?mentioned antibiotic resistance. The RE values of adeB gene mRNA of efflux pump were significantly different in the following antibiotics （AMK， IPM， CFP， FEP， TZP， CAZ， CIP， SCF， CN） between NS groups and S groups respectively. The RE values of efflux pump genes （adeJ， adeG， craA， abeM and amvA） in the two groups had no elevation， and there was no statistical difference between the two groups by comparative analysis. The average RE values of OMP genes （omp25， omp33?36， carO） were all more than 1.0， indicating an increasing of relative expression. Conclusion The A. baumannii is highly resistant to many kinds of antibiotics. The overexpression of efflux pump gene adeB plays an important role in drug resistance of A. baumannii in our hospital， while other efflux pump genes （adeJ、adeG、craA、abeM、amvA） and OMP genes （omp25， omp33?36， carO） may not effect in most isolates of the drug resistance mechanism in this study.

Key words： Acinetobacter baumannii; drug resistance; efflux pump; outer membrane protein

Cite this article

Yubo HUANG , Yuqi ZHOU , Wenzheng ZHENG , Jiaxin ZHU , Hailing YANG , Wenbin WU , Tiantuo. ZHANG . Analysis of efflux pump and outer membrane protein of multi⁃drug resistant Acinetobacter baumannii[J]. The Journal of Practical Medicine, 2023 , 39(16) : 2122 -2129 . DOI: 10.3969/j.issn.1006-5725.2023.16.019

References

1 YOON E J， CHABANE Y N， GOUSSARD S， et al. Contribution of resistance-nodulation-cell division efflux systems to antibiotic resistance and biofilm formation in Acinetobacter baumannii［J］. mBio， 2015，6（2）： e00309-15.
2 ANTUNES L C， VISCA P， TOWNER K J. Acinetobacter baumannii： evolution of a global pathogen［J］. Pathog Dis， 2014，71（3）： 292-301.
3 MARAGAKIS L L， PERL T M. Antimicrobial Resistance： Acinetobacter baumannii： Epidemiology， Antimicrobial Resistance， and Treatment Options［J］. Clin Infect Dis， 2008，46（8）： 1254-1263.
4 TACCONELLI E， CARRARA E， SAVOLDI A， et al. Discovery， research， and development of new antibiotics： the WHO priority list of antibiotic-resistant bacteria and tuberculosis［J］. Lancet Infect Dis， 2018，18（3）： 318-327.
5 ZHANG Z， MORGAN C E， BONOMO R A， et al. Cryo-EM Determination of Eravacycline-Bound Structures of the Ribosome and the Multidrug Efflux Pump AdeJ of Acinetobacter baumannii［J］. mBio， 2021，12（3）： e103121.
6 ABDI S N， GHOTASLOU R， GANBAROV K， et al. Acinetobacter baumannii Efflux Pumps and Antibiotic Resistance［J］. Infect Drug Resist， 2020，13： 423-434.
7 MUNOZ-PRICE L S， WEINSTEIN R A. Acinetobacter infection［J］. N Engl J Med， 2008，358（12）： 1271-1281.
8 HIGGINS P G， WISPLINGHOFF H， KRUT O， et al. A PCR-based method to differentiate between Acinetobacter baumannii and Acinetobacter genomic species 13TU［J］. Clin Microbiol Infect， 2007，13（12）： 1199-1201.
9 HIGGINS P G， LEHMANN M， WISPLINGHOFF H， et al. gyrB Multiplex PCR To Differentiate between Acinetobacter calcoaceticus and Acinetobacter Genomic Species 3［J］. J Clin Microbiol， 2010，48（12）： 4592-4594.
10 CLSI. Performance Standards for Antimicrobial Susceptibility Testing， Twenty-Second Informational Supplement ［S］. PA： Wayne， 2012.
11 COYNE S， GUIGON G， COURVALIN P， et al. Screening and Quantification of the Expression of Antibiotic Resistance Genes in Acinetobacter baumannii with a Microarray［J］. Antimicrob Agents Chemother， 2010，54（1）： 333-340.
12 COYNE S， ROSENFELD N， LAMBERT T， et al. Overexpression of Resistance-Nodulation-Cell Division Pump AdeFGH Confers Multidrug Resistance inAcinetobacter baumannii［J］. Antimicrob Agents Chemother， 2010，54（10）： 4389-4393.
13 RUMBO C， GATO E， LóPEZ M， et al. Contribution of Efflux Pumps， Porins， and β-Lactamases to Multidrug Resistance in Clinical Isolates of Acinetobacter baumannii［J］. Antimicrob Agents Chemother， 2013，57（11）： 5247-5257.
14 YOON E， COURVALIN P， GRILLOT-COURVALIN C. RND-Type Efflux Pumps in Multidrug-Resistant Clinical Isolates of Acinetobacter baumannii： Major Role for AdeABC Overexpression and AdeRS Mutations［J］. Antimicrob Agents Chemother， 2013，57（7）： 2989-2995.
15 HARDING C M， HENNON S W， FELDMAN M F. Uncovering the mechanisms of Acinetobacter baumannii virulence［J］. Nat Rev Microbiol， 2018，16（2）： 91-102.
16 GIAMMANCO A， CALA C， FASCIANA T， et al. Global Assessment of the Activity of Tigecycline against Multidrug-Resistant Gram-Negative Pathogens between 2004 and 2014 as Part of the Tigecycline Evaluation and Surveillance Trial［J］. mSphere， 2017，2（1）： e00310-16.
17 PEREZ S， INNES G K， WALTERS M S， et al. Increase in Hospital-Acquired Carbapenem-Resistant Acinetobacter baumannii Infection and Colonization in an Acute Care Hospital During a Surge in COVID-19 Admissions-New Jersey， February-July 2020［J］. MMWR Morb Mortal Wkly Rep， 2020，69（48）： 1827-1831.
18 胡付品， 朱德妹， 汪复， 等. 2014年CHINET中国细菌耐药性监测［J］. 中国感染与化疗杂志， 2015， 15（5）： 401-410.
19 胡付品， 郭燕， 朱德妹， 等. 2021年CHINET中国细菌耐药监测［J］. 中国感染与化疗杂志， 2022，22（5）： 521-530.
20 VERMA P， TIWARI M， TIWARI V. Efflux pumps in multidrug-resistant Acinetobacter baumannii： Current status and challenges in the discovery of efflux pumps inhibitors［J］. Microb Pathog， 2021，152： 104766.
21 NOWAK J， SCHNEIDERS T， SEIFERT H， et al. The Asp20-to-Asn Substitution in the Response Regulator AdeR Leads to Enhanced Efflux Activity of AdeB in Acinetobacter baumannii［J］. Antimicrob Agents Chemother， 2016，60（2）： 1085-1090.
22 DAMIER-PIOLLE L， MAGNET S， BRE?MONT S， et al. AdeIJK， a Resistance-Nodulation-Cell Division Pump Effluxing Multiple Antibiotics in Acinetobacter baumannii［J］. Antimicrob Agents Chemother， 2008，52（2）： 557-562.
23 POURNARAS S， MARKOGIANNAKIS A， IKONOMIDIS A， et al. Outbreak of multiple clones of imipenem-resistant Acinetobacter baumannii isolates expressing OXA-58 carbapenemase in an intensive care unit［J］. J Antimicrob Chemother， 2006，57（3）： 557-561.
24 WIECZOREK P， SACHA P， CZABAN S， et al. Distribution of AdeABC efflux system genes in genotypically diverse strains of clinical Acinetobacter baumannii［J］. Diagn Microbiol Infect Dise， 2013，77（2）： 106-109.
25 COYNE S， COURVALIN P， PE?RICHON B. Efflux-Mediated Antibiotic Resistance in Acinetobacter spp［J］. Antimicrob Agents Chemother， 2011，55（3）： 947-953.
26 LIN L， LING B， LI X. Distribution of the multidrug efflux pump genes， adeABC， adeDE and adeIJK， and class 1 integron genes in multiple-antimicrobial-resistant clinical isolates of Acinetobacter baumannii-Acinetobacter calcoaceticus complex［J］. Int J Antimicrob Agents， 2009，33（1）： 27-32.
27 SEN B， JOSHI S G. Studies on Acinetobacter baumannii involving multiple mechanisms of carbapenem resistance［J］. J Appl Microbiol， 2016，120（3）： 619-629.
28 ALMASAUDI S B. Acinetobacter spp. as nosocomial pathogens： Epidemiology and resistance features［J］. Saudi J Biol Sci， 2018，25（3）： 586-596.
29 HOU P F， CHEN X Y， YAN G F， et al. Study of the Correlation of Imipenem Resistance with Efflux Pumps AdeABC， AdeIJK， AdeDE and AbeM in Clinical Isolates of Acinetobacter baumannii［J］. Chemotherapy， 2012，58（2）： 152-158.
30 UPPALAPATI S R， SETT A， PATHANIA R. The Outer Membrane Proteins OmpA， CarO， and OprD of Acinetobacter baumannii Confer a Two-Pronged Defense in Facilitating Its Success as a Potent Human Pathogen［J］. Front Microbiol， 2020，11： 589234.
31 BOU G， CERVERO G， DOMINGUEZ M A， et al. Characterization of a nosocomial outbreak caused by a multiresistant Acinetobacter baumannii strain with a carbapenem-hydrolyzing enzyme： high-level carbapenem resistance in A. baumannii is not due solely to the presence of beta-lactamases［J］. J Clin Microbiol， 2000，38（9）： 3299-3305.
32 DEL M T M， BECEIRO A， PEREZ A， et al. Cloning and functional analysis of the gene encoding the 33- to 36-kilodalton outer membrane protein associated with carbapenem resistance in Acinetobacter baumannii［J］. Antimicrob Agents Chemother， 2005，49（12）： 5172-5175.
33 MUSSI M A， LIMANSKY A S， VIALE A M. Acquisition of resistance to carbapenems in multidrug-resistant clinical strains of Acinetobacter baumannii： natural insertional inactivation of a gene encoding a member of a novel family of beta-barrel outer membrane proteins［J］. Antimicrob Agents Chemother， 2005，49（4）： 1432-1440.
34 FERNANDEZ-CUENCA F， SMANI Y， GOMEZ-SANCHEZ M C， et al. Attenuated virulence of a slow-growing pandrug-resistant Acinetobacter baumannii is associated with decreased expression of genes encoding the porins CarO and OprD-like［J］. Int J Antimicrob Agents， 2011，38（6）： 548-549.
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