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

Infective endocarditis (IE) caused by 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 but here we describe the first reported IE relapse with more than a year (17 months) af...

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Bibliographic Details
Published in:Antimicrobial agents and chemotherapy 2024-03, Vol.68 (3), p.e0108323
Main Authors: Ortiz de la Rosa, José Manuel, Martín-Gutiérrez, Guillermo, Casimiro-Soriguer, Carlos S, Gimeno-Gascón, María Adelina, Cisneros, José Miguel, de Alarcón, Arístides, Lepe, José Antonio
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Language:English
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Summary:Infective endocarditis (IE) caused by 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 but here we describe the first reported IE relapse with 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 , 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 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 and the late relapse of the IE. These data represent the first clinical evidence of mutations in the stringent response ( gene) related with IE relapse.
ISSN:0066-4804
1098-6596
1098-6596
DOI:10.1128/aac.01083-23