Integrative and conjugative elements carrying high-level gentamicin resistance genes in Streptococcus dysgalactiae subsp. equisimilis from horses.

Overview

• This study investigated the presence and characteristics of high-level gentamicin resistance (HLGR) in Streptococcus dysgalactiae subsp. equisimilis strains isolated from horses, focusing on the genetic elements responsible for resistance and their potential for transfer to other bacteria.

Background and Medical Importance

• Gentamicin is an antibiotic that, when combined with beta-lactams, shows synergy effective for treating severe infections like endocarditis.
• In streptococci, the acquisition of high-level gentamicin resistance (HLGR) disrupts this valuable synergy, posing a medical concern.
• HLGR has been mainly studied in group B Streptococci, where it is associated with the bifunctional gene aac(6’)-aph(2”), conferring resistance.

Study Focus and Isolates

• HLGR was studied in Streptococcus dysgalactiae subsp. equisimilis strains isolated from the uterus of mares during routine pre-fecundation screenings.
• One strain was also isolated from a mare’s lymph node.
• The mares were from six different horse studs located in four administrative departments in France.
• The HLGR isolates belonged to three sequence types (STs): ST196 (26 isolates), ST223 (1 isolate), and a single locus variant (SLV) of ST200 (1 isolate).

Genetic Basis of HLGR

• This study identified, for the first time, HLGR mediated by the two genes aph(2’’)-Ib and aac(6’)-Im located on a class 5 integrative mobilizable element (IME), named HLGR_IME.
• In isolates belonging to ST196 and ST223, the HLGR_IME was inserted into a Tn-type transposon.
• In the isolate assigned to an ST200-SLV, the HLGR_IME was inserted into an integrative and conjugative element (ICE)-type element.

Transfer and Mobility of Resistance

• The Tn-type transposon harboring HLGR_IME was capable of transferring gentamicin resistance from HLGR Streptococcus dysgalactiae to an erythromycin-resistant recipient strain.
• This transferability highlights a risk of spreading HLGR genes to human pathogens, including Streptococcus species.

Phylogenetic Findings

• Phylogenetic analysis showed that Streptococcus dysgalactiae strains from horses formed a distinct clade, separate from strains isolated from humans or other animals.
• This uniqueness suggests adaptation or specialization of these strains in the equine environment.

Dissemination within Horse Populations

• HLGR strains belonging to ST196 were shown to disseminate among mares within a single stud over a two-year period.
• This particular clone had also been reported previously in the USA, indicating an international spread.

Implications and Recommendations

• The ability of HLGR genes to transfer between streptococci raises concerns for both veterinary and human health.
• Hygiene measures in veterinary settings are important to prevent further spread of HLGR streptococci among horses.
• Preventing dissemination may help preserve the efficacy of gentamicin-beta-lactam synergy and reduce the risk of HLGR spreading to important pathogens.