Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>

The rise of antibiotic-resistant bacteria is among the biggest challenges in human and veterinary medicine. One of the major factors that contributes to resistance is use of frontline clinical antibiotics in veterinary practices. To avoid this problem, searching for antimicrobials aimed at veterinar...

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Main Authors: Kirill V. Ovchinnikov, Christian Kranjec, Tage Thorstensen, Harald Carlsen, Dzung B. Diep
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/11/12/1691
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author Kirill V. Ovchinnikov
Christian Kranjec
Tage Thorstensen
Harald Carlsen
Dzung B. Diep
author_facet Kirill V. Ovchinnikov
Christian Kranjec
Tage Thorstensen
Harald Carlsen
Dzung B. Diep
author_sort Kirill V. Ovchinnikov
collection DOAJ
description The rise of antibiotic-resistant bacteria is among the biggest challenges in human and veterinary medicine. One of the major factors that contributes to resistance is use of frontline clinical antibiotics in veterinary practices. To avoid this problem, searching for antimicrobials aimed at veterinary applications is becoming especially important. Thiopeptide micrococcin P1 and leaderless peptide EntEJ97s are two different bacteriocins that are very active against many gram-positive bacteria; however, sensitive bacteria can rapidly develop resistance towards those bacteriocins. To overcome this problem, we searched for synergy between those bacteriocins and conventional antibiotics against methicillin-resistant <i>Staphylococcus pseudintermedius</i> (MRSP): a common pathogen in animal skin infections. The two bacteriocins acted synergistically with each other and with penicillin G against MRSP clinical isolates in both planktonic and biofilm assays; they also prevented resistance development. The therapeutic potential was further validated in a murine skin infection model that showed that a combination of micrococcin P1, EntEJ97s and penicillin G reduced cell-forming units of MRSP by 2-log<sub>10</sub> CFU/g. Taken together, our data show that a combination of bacteriocins with conventional antibiotics can not only prevent resistance development but also pave the way to revitalize some old, less useful antibiotics, such as penicillin, which by itself has no effect on methicillin-resistant pathogens.
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spelling doaj.art-8b4a80925c3c4f2e80912a62726d1ef62023-11-24T12:52:44ZengMDPI AGAntibiotics2079-63822022-11-011112169110.3390/antibiotics11121691Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>Kirill V. Ovchinnikov0Christian Kranjec1Tage Thorstensen2Harald Carlsen3Dzung B. Diep4Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, NorwayDepartment of Plant Molecular Biology, Norwegian Institute of Bioeconomy Research, 1431 Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, NorwayFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1430 Ås, NorwayThe rise of antibiotic-resistant bacteria is among the biggest challenges in human and veterinary medicine. One of the major factors that contributes to resistance is use of frontline clinical antibiotics in veterinary practices. To avoid this problem, searching for antimicrobials aimed at veterinary applications is becoming especially important. Thiopeptide micrococcin P1 and leaderless peptide EntEJ97s are two different bacteriocins that are very active against many gram-positive bacteria; however, sensitive bacteria can rapidly develop resistance towards those bacteriocins. To overcome this problem, we searched for synergy between those bacteriocins and conventional antibiotics against methicillin-resistant <i>Staphylococcus pseudintermedius</i> (MRSP): a common pathogen in animal skin infections. The two bacteriocins acted synergistically with each other and with penicillin G against MRSP clinical isolates in both planktonic and biofilm assays; they also prevented resistance development. The therapeutic potential was further validated in a murine skin infection model that showed that a combination of micrococcin P1, EntEJ97s and penicillin G reduced cell-forming units of MRSP by 2-log<sub>10</sub> CFU/g. Taken together, our data show that a combination of bacteriocins with conventional antibiotics can not only prevent resistance development but also pave the way to revitalize some old, less useful antibiotics, such as penicillin, which by itself has no effect on methicillin-resistant pathogens.https://www.mdpi.com/2079-6382/11/12/1691bacteriocinantibioticsMRSPskin infectionantibiotic resistance
spellingShingle Kirill V. Ovchinnikov
Christian Kranjec
Tage Thorstensen
Harald Carlsen
Dzung B. Diep
Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
Antibiotics
bacteriocin
antibiotics
MRSP
skin infection
antibiotic resistance
title Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
title_full Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
title_fullStr Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
title_full_unstemmed Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
title_short Bacteriocins Revitalize Non-Effective Penicillin G to Overcome Methicillin-Resistant <i>Staphylococcus pseudintermedius</i>
title_sort bacteriocins revitalize non effective penicillin g to overcome methicillin resistant i staphylococcus pseudintermedius i
topic bacteriocin
antibiotics
MRSP
skin infection
antibiotic resistance
url https://www.mdpi.com/2079-6382/11/12/1691
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AT christiankranjec bacteriocinsrevitalizenoneffectivepenicillingtoovercomemethicillinresistantistaphylococcuspseudintermediusi
AT tagethorstensen bacteriocinsrevitalizenoneffectivepenicillingtoovercomemethicillinresistantistaphylococcuspseudintermediusi
AT haraldcarlsen bacteriocinsrevitalizenoneffectivepenicillingtoovercomemethicillinresistantistaphylococcuspseudintermediusi
AT dzungbdiep bacteriocinsrevitalizenoneffectivepenicillingtoovercomemethicillinresistantistaphylococcuspseudintermediusi