Find in Library

Neonatal infection is a significant cause of mortality and morbidity in infants. The global incidence of multi-drug resistance continues to rise among neonatal pathogens, indicating a need for alternative treatment strategies. Nisin is an antimicrobial peptide that exhibits broad-spectrum activity against a wide variety of clinical pathogens and can be used in combination with antibiotics to improve their effectiveness. This study examined the activity of nisin and bioengineered derivatives against multi-drug resistant <i>Streptococcus agalactiae</i> and <i>Staphylococcus capitis</i> isolates and investigated the potential synergy between nisin peptides and selected antibiotics. Whole genome sequence analysis of the strains revealed the presence of multi-drug resistant determinants, e.g., macrolide, tetracycline, β-lactam, aminoglycoside, while the <i>S. agalactiae</i> strains all possessed both <i>nsr</i> and <i>nsr</i>FP genes and the <i>S. capitis</i> strains were found to encode the <i>nsr</i> gene alone. Deferred antagonism assays demonstrated that nisin PV had improved antimicrobial activity against all strains tested (<i>n</i> = 10). The enhanced specific activity of this peptide was confirmed using minimum inhibitory concentrations (MIC) (0–4-fold lower MIC for nisin PV) and broth-based survival assays. Combinations of nisin peptides with antibiotics were assessed for enhanced antimicrobial activity using growth and time-kill assays and revealed a more effective nisin PV/ampicillin combination against one <i>S. capitis</i> strain while a nisin A/erythromycin combination displayed a synergistic effect against one <i>S. agalactiae</i> strain. The findings of this study suggest that nisin derivatives alone and in combination with antibiotics have potential as alternative antimicrobial strategies to target neonatal pathogens.