Clinical Staphylococcus argenteus Develops to Small Colony Variants to Promote Persistent Infection

Abstract

<i>Staphylococcus argenteus</i> is a novel staphylococcal species (also considered as a part of <i>Staphylococcus aureus</i> complex) that is infrequently reported on, and clinical <i>S. argenteus</i> infections are largely unstudied. Here, we report a persistent and recurrent hip joint infection case in which a <i>S. argenteus</i> strain and its small colony variants (SCVs) strain were successively isolated. We present features of the two <i>S. argenteus</i> strains and case details of their pathogenicity, explore factors that induce <i>S. argenteus</i> SCVs formation in the course of anti-infection therapy, and reveal potential genetic mechanisms for <i>S. argenteus</i> SCVs formation. <i>S. argenteus</i> strains were identified using phenotypic and genotypic methods. The <i>S. argenteus</i> strain XNO62 and SCV strain XNO106 were characterized using different models. <i>S. argenteus</i> SCVs were induced by the administration of amikacin and by chronic infection course based on the clinical case details. The genomes of both strains were sequenced and aligned in a pair-wise fashion using Mauve. The case details gave us important insights on the characteristics and therapeutic strategies for infections caused by <i>S. argenteus</i> and its SCVs. We found that strain XNO62 and SCV strain XNO106 are genetically-related sequential clones, the SCV strain exhibits reduced virulence but enhanced intracellular persistence compared to strain XNO62, thus promoting persistent infection. The induction experiments for <i>S. argenteus</i> SCVs demonstrated that high concentrations of amikacin greatly induce <i>S. argenteus</i> XNO62 to form SCVs, while a chronic infection of <i>S. argenteus</i> XNO62 slightly induces SCVs formation. Potential genetic mechanisms for <i>S. argenteus</i> SCVs formation were revealed and discussed based on genomic alignments. In conclusion, we report the first case of infection caused by <i>S. argenteus</i> and its SCVs strain. More attention should be paid to infections caused by <i>S. argenteus</i> and its SCVs, as they constitute a challenge to current therapeutic strategies. The problem of <i>S. argenteus</i> SCVs should be noticed, in particular when amikacin is used or in the case of a chronic <i>S. argenteus</i> infection.