Antibacterial Activity of Peptide Derivatives of Phosphinothricin against Multidrug-Resistant Klebsiella pneumoniae.

The fast spread of bacteria that are resistant to many classes of antibiotics (multidrug resistant) is a global threat to human and animal health with a worrisome scenario ahead. Novel therapeutical strategies are of crucial importance to combat this phenomenon. For this purpose, we investigated the antimicrobial properties of the naturally occurring tripeptide Bialaphos and a dipeptide L-leucyl-L-phosphinoithricin, the synthesis and diastereomers separation of which are herein described. We demonstrate that these compounds are effective on clinical isolates of the human pathogen Klebsiella pneumoniae, causing hospital-acquired and community-acquired infections. The tested isolates were remarkable for their resistance to more than 20 commercial antibiotics of different classes. Based on previous literature data and our experiments consisting of glutamine supplementation, we suggest that both compounds release phosphinothricin-a well-known nanomolar inhibitor of glutamine synthetase-after their penetration in the bacterial cells; and, in this way, exert their antibacterial effect by negatively affecting nitrogen assimilation in this pathogen.

Emergence of Five Genetic Lines ST395NDM-1, ST13OXA-48, ST3346OXA-48, ST39CTX-M-14, and Novel ST3551OXA-48 of Multidrug-Resistant Clinical Klebsiella pneumoniae in Russia.

Aims: The objective of this study was phenotypic and genotypic characterization of antibacterial-resistant Klebsiella pneumoniae clinical strains isolated in Moscow Transplantology Intensive Care Unit in 2017-2019. Results: Major strains among K. pneumoniae (n = 63) isolated from 30 patients were recognized as extensive drug-resistant (n = 55) pathogens, and remaining strains were recognized as multidrug-resistant (n = 8) pathogens. The beta-lactamase genes blaSHV-1,-2a,-11,-27,-67,-187 (n = 63), blaCTX-M-14,-15 (n = 61), blaTEM-1 (n = 54), blaOXA-48 (n = 52), and blaNDM-1 (n = 2), as well as class 1 integrons (n = 19) carried gene cassette arrays aacA4 (n = 2), dfrA1-orfC (n = 6), aadB-aadA1 (n = 9), dfrA15-aadA1 (n = 3), and dfrA12-orfF-aadA2 (n = 1) were identified in the strains. All strains carried four virulence genes: wabG, fimH, uge, and allS, but two strains had additionally kfu gene. Six known sequence types (STs) of K. pneumoniae ST395 (n = 44), ST377 (n = 3), ST307 (n = 4), ST13 (n = 2), ST39 (n = 2), ST3346 (n = 1), and a novel sequence-type ST3551 (n = 7) were identified. Phylogenetic analysis showed that ST3551 belonged to the cluster of clonal group CG147, and the remaining six STs to the another cluster consisting of four subgroups. The emergence of K. pneumoniae genetic lines carrying epidemiologically significant beta-lactamase genes ST395NDM-1, ST13OXA-48, ST3346OXA-48/CTX-M-14, ST3551OXA-48, and ST39CTX-M-14 was the first case of detection in Russia. Conclusion: The emergence of novel carbapenemase-producing K. pneumoniae genetic lines in Russia highlights the global negative tendency of multidrug-resistant pathogens spread in high-technological medical centers.