Broad and Efficient Control of Klebsiella Pathogens by Peptidoglycan-Degrading and Pore-Forming Bacteriocins Klebicins

Abstract

Gram-negative bacteria belonging to the genus Klebsiella are important nosocomial pathogens, readily acquiring resistance to all known antibiotics. Bacteriocins, non-antibiotic antibacterial proteins, have been earlier proposed as potential therapeutic agents for control of other Gram-negative species such as Escherichia, Pseudomonas and Salmonella. This study is the first report describing pore-forming and peptidoglycan-degrading bacteriocins klebicins from Klebsiella. We have identified, cloned, expressed in plants and characterized nine pore-forming and peptidoglycan-degrading bacteriocins from different Klebsiella species. We demonstrate that klebicins can be used for broad and efficient control of 101 of the 107 clinical isolates representing five Klebsiella species, including multi-drug resistant pathovars and pathovars resistant to carbapenem antibiotics.

Bacteriocins: An Overview of Antimicrobial, Toxicity, and Biosafety Assessment by in vivo Models

“…As expected, bacteriocins have an outstanding record to kill or reduce pathogens and drug-resistant pathogens during in vitro assessments (Fuchs et al, 2011;Cui et al, 2012;Gabrielsen et al, 2014;Ishibashi et al, 2014;Al Atya et al, 2016;Jiang et al, 2017;Aguilar-Pérez et al, 2018;Ansari et al, 2018;Denkovskienė et al, 2019;Peng et al, 2019;Newstead et al, 2020). Conventionally, bacteriocins display a non-toxic behavior at in vitro assays (Cebrián et al, 2019).…”

“…Pentocin JL-1 has also been demonstrated to have antibacterial activity against Gram-positive and Gram-negative bacteria, particularly MDR S. aureus ( Jiang et al, 2017 ). Other examples, such as the novel entianin, which has activity against MRSA (ATCC 43300) and vancomycin-resistant Enterococcus faecalis (ATCC 51299) strains ( Fuchs et al, 2011 ), and bacteriocins klebicins have been demonstrated to be active against MDR and carbapenem-resistant Klebsiella species ( Denkovskienė et al, 2019 ). Moreover, novel enterocins DD28 and DD93 showed anti-staphylococcal activity in MRSA ( Al Atya et al, 2016 ).…”

The Biology of Colicin M and Its Orthologs

“…As mentioned above, several orthologs of ColM, which are produced by Pseudomonas spp., Pectobacterium carotovorum , Burkholderia spp. and Klebsiella species, have been identified [ 50 , 51 , 52 , 53 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ]. These orthologs present a high sequence similarity with the C-terminal domain of ColM ( Figure 9 ) and some of them have been biochemically and/or structurally characterized, as it will be discussed below.…”

“…Different ColM orthologs from genus Pseudomonas spp. have been identified and characterized [ 50 , 62 , 67 , 69 ]. These are PaeM1, PaeM2, PflM and PsyM, that have been found in P. aeruginosa JJ692, P. aeruginosa NCTC10332, P. syringae pv.…”

“…BLAST search followed by amino acid sequence alignment led to the identification of four putative ColM-like proteins: KpneM from K. pneumoniae EWD35590.1, KpneM2 from Klebsiella sp. WP_047066220, KvarM from K. variicola CTQ17225.1 and KaerM from K. aerogenes WP_015367360.1, displaying 48, 42, 43 and 29% sequence identity with ColM, respectively [ 67 ].…”