Activation of class 1 integron integrase is promoted in the intestinal environment

Murielle Baltazar (1, 2, 3) , Nadège Bourgeois-Nicolaos (4, 5) , Macarena Larroudé (4) , William Couet (6, 7, 8) , Solange Uwajeneza (4) , Florence Doucet-Populaire (4) , Marie-Cécile Ploy (1, 2, 3) , Sandra da Re (1, 2, 3)

1 RESINFIT - Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques
2 UNILIM - Université de Limoges
3 CHU Limoges
4 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
5 AP-HP - Hôpital Antoine Béclère [Clamart]
6 PHAR2 [Poitiers] - Pharmacologie des anti-infectieux et antibiorésistance [U 1070]
7 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
8 Université de Poitiers - Faculté de Médecine et de Pharmacie

Class 1 integrons are widespread genetic elements playing a major role in the dissemination of antibiotic resistance. They allow bacteria to capture, express and exchange antibiotic resistance genes embedded within gene cassettes. Acquisition of gene cassettes is catalysed by the class 1 integron integrase, a site-specific recombinase playing a key role in the integron system. In in vitro planktonic culture, expression of intI1 is controlled by the SOS response, a regulatory network which mediates the repair of DNA damage caused by a wide range of bacterial stress, including antibiotics. However, in vitro experimental conditions are far from the real lifestyle of bacteria in natural environments such as the intestinal tract which is known to be a reservoir of integrons. In this study, we developed an in vivo model of intestinal colonization in gnotobiotic mice and used a recombination assay and quantitative real-time PCR, to investigate the induction of the SOS response and expression and activity of the class 1 integron integrase, IntI1. We found that the basal activity of IntI1 was higher in vivo than in vitro . In addition, we demonstrated that administration of a subinhibitory concentration of ciprofloxacin rapidly induced both the SOS response and intI1 expression that was correlated with an increase of the activity of IntI1. Our findings show that the gut is an environment in which the class 1 integron integrase is induced and active, and they highlight the potential role of integrons in the acquisition and/or expression of resistance genes in the gut, particularly during antibiotic therapy.

Domaines: Microbiologie et Parasitologie

Murielle Baltazar, Nadège Bourgeois-Nicolaos, Macarena Larroudé, William Couet, Solange Uwajeneza, et al.. Activation of class 1 integron integrase is promoted in the intestinal environment. PLoS Genetics, 2022, 18 (4), pp.e1010177. ⟨10.1371/journal.pgen.1010177⟩. ⟨hal-03906694⟩