Title :

Assessing the threat of Yersinia pestis harboring a multi-resistant IncC plasmid and the efficacy of an antibiotic targeting LpxC

Author(s) :

Lemaitre, Nadine [Auteur]
Laboratoire de parasitologie et de mycologie médicales [CHU Amiens]
Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 [AGIR ]
Dewitte, Amélie [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Rakotomanimana, Faniry [Auteur]
Gooden, David [Auteur]
Toone, Eric [Auteur]
Rajerison, Minoarisoa [Auteur]
Université d'Antananarivo
Unité Peste - Plague Unit [Antananarivo, Madagascar]
Zhou, Pei [Auteur]
Sebbane, Florent [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

Antimicrobial Agents and Chemotherapy

Publisher :

American Society for Microbiology

Publication date :

2025-01-30

ISSN :

0066-4804

English keyword(s) :

Flea
LpxC
Rodents
Yersinia pestis
drug targets
multidrug resistance
plague
plasmid-mediated resistance
virulence

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses

English abstract : [en]

Self-transmissible IncC plasmids rapidly spread multidrug resistance in many medically important pathogens worldwide. A large plasmid of this type (pIP1202, ~80 Kb) has been isolated in a clinical isolate of Yersinia pestis ...
Show more >Self-transmissible IncC plasmids rapidly spread multidrug resistance in many medically important pathogens worldwide. A large plasmid of this type (pIP1202, ~80 Kb) has been isolated in a clinical isolate of Yersinia pestis , the agent of plague. Here, we report that pIP1202 was highly stable in Y. pestis- infected mice and fleas and did not reduce Y. pestis virulence in these animals. Although pIP1202 inflicted a fitness cost in fleas (but not in mice) when the insects fed on blood containing a mixture of plasmid-free and plasmid-bearing strains, such a co-infection scenario has never been reported in nature, indicating that pIP1202 could persist in Y. pestis strains. Despite being resistant to commonly used antibiotic treatments, we show that plague caused by Y. pestis harboring the pIP1202 plasmid is effectively cured by LPC-233—a potent inhibitor of the essential LpxC enzyme in the lipid A biosynthetic pathway. Taken as a whole, our data highlight the alarming threat posed by Y. pestis harboring multidrug-resistant IncC plasmids that may persist in wild animals as a reservoir for long periods without antibiotic pressure and illuminate the impact of antibiotics with a novel mode of action against such a biothreat.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL