Role of SHV-11, a Class A β-Lactamase, Gene in Multidrug Resistance Among Klebsiella pneumoniae Strains and Understanding Its Mechanism by Gene Network Analysis

Microb Drug Resist. 2020 Aug;26(8):900-908. doi: 10.1089/mdr.2019.0430. Epub 2020 Mar 2.

Abstract

Aim: The rapid emergence of β-lactam resistance in gram-negative bacteria is a major problem in the treatment of infections caused by pathogenic bacterial strains, in particular Klebsiella pneumoniae. In our study, we are presenting a systems biology approach to understand the role of SHV-11 gene in drug resistance mechanism patterns in K. pneumoniae strain. Results: From the results, we have observed that the SHV-11 gene has a role in drug resistance mechanism along with its functional partner genes gyrA, parC, glsA, osmE, yjhA, yhdT, rimL, pepB, KPN_00437, and KPN_01875. We have also observed that of 51 genes, 27 genes were enriched in various Gene Ontology terms such as DNA metabolic process, DNA repair, and response to stress. The genes gyrA, parC, gyrB, parE, recA, dnaA, polB, dnaK, mutS, and dnaN constitute >41% of the total interactions; thus, these genes can be considered as hub nodes in the network, and they can be used as the potential drug targets. Conclusions: Drug exposure leads to the DNA damage in bacterial spp. We observed that the SHV11 gene along with the functional partners help in maintaining the genomic integrity by withstanding the environmental stress by inducing DNA damage repair mechanism. Our results provide a detailed understanding on the role of SHV-11 gene in drug resistance mechanisms in K. pneumoniae, and we are of the opinion that our results will be useful for researchers exploring the antibiotic resistance mechanisms in pathogenic bacteria.

Keywords: Gene Ontology; Klebsiella pneumoniae; SHV-11; antimicrobial resistance; gene interaction network.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • DNA Damage / drug effects
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Epistasis, Genetic / drug effects
  • Epistasis, Genetic / genetics
  • Genes, Bacterial / drug effects
  • Genes, Bacterial / genetics
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Microbial Sensitivity Tests
  • beta-Lactam Resistance / drug effects
  • beta-Lactam Resistance / genetics*
  • beta-Lactamases / drug effects
  • beta-Lactamases / genetics*

Substances

  • Anti-Bacterial Agents
  • beta-lactamase SHV-11
  • beta-Lactamases