Mechanism of High-Level Daptomycin Resistance in Corynebacterium striatum

Abstract

Antimicrobial resistance threatens the efficacy of antimicrobial treatment options, including last-line-of-defense drugs. Understanding how this resistance develops can help direct antimicrobial stewardship efforts and is critical to designing the next generation of antimicrobial therapies. Here we determine how Corynebacterium striatum, a skin commensal and opportunistic pathogen, evolved high-level resistance to a drug of last resort, daptomycin. Through a single mutation, this pathogen was able to remove the daptomycin’s target, phosphatidylglycerol (PG), from the membrane and evade daptomycin’s bactericidal activity. We found that additional compensatory changes were not necessary to support the removal of PG and replacement with phosphatidylinositol (PI). The ease with which C. striatum evolved high-level resistance is cause for alarm and highlights the importance of screening new antimicrobials against a wide range of clinical pathogens which may harbor unique capacities for resistance evolution.

Mutations in cdsA and pgsA Correlate with Daptomycin Resistance in Streptococcus mitis and S. oralis

“…Nevertheless, our effort to introduce a mutated pgsA into an S. oralis isolate resulted in a DAP-R phenotype. Although we cannot rule out changes in other genes that contribute to the phenotype, our results and others published previously confirm the link between pgsA and DAP-R (12,13,20). Our data also suggest the occurrence of multiple pathways of phospholipid adaptation leading to marked changes in cell membrane content of streptococci on antibiotic challenge.…”

Infective Endocarditis Due to Corynebacterium Species: Clinical Features and Antibiotic Resistance

“…Resistance to rifampicin was also frequent. Similar to our results, resistance in vitro to multiple antimicrobials have been recognized in several studies [ 21 , 22 ]. Regarding therapy for pathogens such as C jeikeium or C striatum vancomycin may therefore be the initial choice of antibiotic therapy.…”

Current Evidence for Corynebacterium on the Ocular Surface

“…All these cases occurred in patients with poorly controlled diabetes, long-term steroid treatment, bullous keratopathy, or Stevens-Johnson syndrome or who used punctal plugs due to severe dry eye disease. The Corynebacterium species were not identified; however, the following genes coding for antibiotic resistance, including quinolones, were found: ermX (macrolides and lincosamides), aphA (aminoglycosides), and cmx (chloramphenicol) [ 47 , 79 , 80 ]. The overuse of antibiotics can drive spontaneous mutation in Corynebacterium species [ 72 , 73 ], thereby causing a prevalence of multidrug-resistant Corynebacterium species.…”