ORCID

0000-0002-1778-3238

Department

Biological Sciences

Year of Study

3

Full-time or Part-time Study

Full-time

Level

Postgraduate

Presentation Type

Poster

Supervisor

Dr. Fiona O'Halloran

Supervisor

Dr. Lesley Cotter

Supervisor

Dr. Des Field

Abstract

Neonatal infection is a significant cause of mortality and morbidity in infants. Globally, neonatal pathogens are increasingly becoming multi-drug resistant, indicating the need to discover novel alternative treatment strategies. Nisin is an antimicrobial peptide that exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria including a wide variety of clinical pathogens. Nisin can be used in combination with antibiotics to improve their efficacy. This study examined the activity of nisin and bioengineered derivatives against multi-drug resistant Streptococcus agalactiae and Staphylococcus capitis 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 in all strains, e.g., macrolide, tetracycline, β-lactam, aminoglycoside. The S. agalactiae strains all possessed both nsr and nsrFP genes and the S. capitis strains were found to encode the nsr gene alone. Deferred antagonism assays demonstrated that nisin PV had improved antimicrobial activity against all strains tested (n = 10). The enhanced specific activity of this peptide was confirmed using minimum inhibitory concentrations (MIC) (0–4-fold lower MIC for nisin PV). 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 S. capitis strain while a nisin A/erythromycin combination displayed a synergistic effect against one S. agalactiae 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.

Keywords:

antibacterial peptide, bioengineered peptide, nisin, Streptococcus agalactiae, Staphylococcus capitis, neonatal infections

Start Date

2-11-2023 11:15 AM

End Date

2-11-2023 12:00 PM

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Nov 2nd, 11:15 AM Nov 2nd, 12:00 PM

Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens

Neonatal infection is a significant cause of mortality and morbidity in infants. Globally, neonatal pathogens are increasingly becoming multi-drug resistant, indicating the need to discover novel alternative treatment strategies. Nisin is an antimicrobial peptide that exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria including a wide variety of clinical pathogens. Nisin can be used in combination with antibiotics to improve their efficacy. This study examined the activity of nisin and bioengineered derivatives against multi-drug resistant Streptococcus agalactiae and Staphylococcus capitis 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 in all strains, e.g., macrolide, tetracycline, β-lactam, aminoglycoside. The S. agalactiae strains all possessed both nsr and nsrFP genes and the S. capitis strains were found to encode the nsr gene alone. Deferred antagonism assays demonstrated that nisin PV had improved antimicrobial activity against all strains tested (n = 10). The enhanced specific activity of this peptide was confirmed using minimum inhibitory concentrations (MIC) (0–4-fold lower MIC for nisin PV). 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 S. capitis strain while a nisin A/erythromycin combination displayed a synergistic effect against one S. agalactiae 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.