C-terminal deletion of RelA protein is suggested as a possible cause of infective endocarditis recurrence with Enterococcus faecium

Author:

Ortiz de la Rosa José Manuel123,Martín-Gutiérrez Guillermo1234ORCID,Casimiro-Soriguer Carlos S.12,Gimeno-Gascón María Adelina12,Cisneros José Miguel1235,de Alarcón Arístides123,Lepe José Antonio1236

Affiliation:

1. Clinical Unit of Infectious Diseases, Microbiology and Parasitology, University Hospital Virgen del Rocío, Seville, Spain

2. Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain

3. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Madrid, Spain

4. Department of Health Sciences, Loyola Andalucía University, Sevilla, Spain

5. Faculty of Medicine, University of Seville, Seville, Spain

6. Department of Microbiology, University of Seville, Seville, Spain

Abstract

ABSTRACT Infective endocarditis (IE) caused by Enterococcus spp. represents the third most common cause of IE, with high rates of relapse compared with other bacteria. Interestingly, late relapses (>6 months) have only been described in Enterococcus faecalis, but here we describe the first reported IE relapse with Enterococcus faecium more than a year (17 months) after the initial endocarditis episode. Firstly, by multi locus sequence typing (MLST), we demonstrated that both isolates (EF646 and EF641) belong to the same sequence type (ST117). Considering that EF641 was able to overcome starvation and antibiotic treatment conditions surviving for a long period of time, we performed bioinformatic analysis in identifying potential genes involved in virulence and stringent response. Our results showed a 13-nucleotide duplication (positions 1638–1650) in the gene relA , resulting in a premature stop codon, with a loss of 167 amino acids from the C-terminal domains of the RelA enzyme. RelA mediates the stringent response in bacteria, modulating levels of the alarmone guanosine tetraphosphate (ppGpp). The relA mutant (EF641) was associated with lower growth capacity, the presence of small colony variants, and higher capacity to produce biofilms (compared with the strain EF646), but without differences in antimicrobial susceptibility patterns according to standard procedures during planktonic growth. Instead, EF641 demonstrated tolerance to high doses of teicoplanin when growing in a biofilm. We conclude that all these events would be closely related to the long-term survival of the E. faecium and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response ( relA gene) related with E. faecium IE relapse.

Funder

MEC | Instituto de Salud Carlos III

Publisher

American Society for Microbiology

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Biofilm-specific determinants of enterococci pathogen;Archives of Microbiology;2024-09-09

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