The mutL Mutation in Pseudomonas aeruginosa Isolates Reveals Multidrug-resistant Traits and Possible Evolutionary Trends

Abstract

To evaluate the genetic differences and possible evolutionary trends of clinical multidrug-resistant (MDR) strains, Pseudomonas aeruginosa isolates were characterized by pulsed-field gel electrophoresis (PFGE) and evolutionary distances were estimated. A total of 85.7% of the P. aeruginosa isolates were MDR strains. Strains with the PFGE pattern A predominated; all were susceptible to amikacin and cefepime but resistant to levofloxacin and meropenem (except strain PA45 which was sensitive to meropenem). PFGE pattern H or P strains exhibited resistance to six to eight different antibiotics. PFGE pattern I or J strains were susceptible to all antibiotics tested. Two imperfect six base-pair tandem repeats, CTGGCG and CTGGCC, were found in the mutL gene. In conclusion, MDR characteristics and PFGE profiles were clearly correlated with the mutL phylogenetic tree. This indicates that mutations in mutL might contribute to genetic stability in adaptation by changing the MDR traits. Phylogenetic analysis of mutL revealed the MDR relatedness of P. aeruginosa strains.

The methylation-independent mismatch repair machinery in Pseudomonas aeruginosa

“…This is somewhat surprising, given that MutL Ec and MutL PA share only 18% amino acid sequence identity in the crucial endonuclease-encoding CTD. This said, most (21/22) of the key amino acid residues known to be important for MutL Ec function are conserved in MutL PA , and the structural framework of the CTD also seems to be conserved between the two proteins [106, 107]. One possibility is that the MutH-independent nicks introduced by MutL PA are sufficient for MMR in E.…”

Effective in Vitro Synergy of Piperacillin/Tazobactam Plus either Netilmicin or Aztreonam against Metallo-β-lactamase-producing Pseudomonas Aeruginosa

“…Pseudomonas aeruginosa is an important opportunistic pathogen that plays a serious role in many infections especially in immuno-compromised patients [1]. Infections by this organism are characterized as severe and resistant to treatment with drugs [2].…”

“…Continued emergence and rapid spread of MDR Ps. aeruginosa strains have resulted in increased morbidity, mortality and cost [1,4]. This increased the need for alternative strategies such as combination of anti-pseudomonal antibiotics as an alternative strategy in the management of these cases.…”