Bioengineered Nisin A Derivatives Display Enhanced Activity against Clinical Neonatal Pathogens.

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 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, e.g., macrolide, tetracycline, ß-lactam, aminoglycoside, while 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) 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 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.

A review of antibiotic resistance in Group B Streptococcus: the story so far.

Group B Streptococcus (GBS) is the leading cause of neonatal disease worldwide, and invasive disease in adults is becoming more prevalent. Currently, some countries adopt an intrapartum antibiotic prophylaxis regime to help prevent the transmission of GBS from mother to neonate during delivery. This precaution has reduced the incidence of GBS-associated early-onset disease; however, rates of late-onset disease and stillbirths associated with GBS infections remain unchanged. GBS is still recognized as being universally susceptible to beta-lactam antibiotics; however, there have been reports of reduced susceptibility to beta-lactams, including penicillin, in some countries. Resistance to second-line antibiotics, such as erythromycin and clindamycin, remains high amongst GBS, with several countries noting increased resistance rates in recent years. Moreover, resistance to other antibiotic classes, such as fluoroquinolones and aminoglycosides, also continues to rise. In instances where patients are allergic to penicillin and second-line antibiotics are ineffective, vancomycin is administered. While vancomycin, a last resort antibiotic, still remains largely effective, there have been two documented cases of vancomycin resistance in GBS. This review provides a comprehensive analysis of the prevalence of antibiotic resistance in GBS and outlines the specific resistance mechanisms identified in GBS isolates to date.

Antistaphylococcal activity of novel salicylanilide derivatives.

This study examined the antibacterial properties of nineteen benzoxazole, isoniazid, ethionamide and salicylanilide derivatives against Staphylococcus aureus (S. aureus). It was found that three salicylanilide-derived compounds demonstrated antistaphylococcal activity: 5-Chloro-2-hydroxy-N-(4-(trifluoromethyl)phenyl)benzamide (5-Cl-4'-CF3- SAL), 4-chloro-2-(3-chlorophenylcarbamyoyl)phenyl)-2-(benzyloxycarbonylamino)propanoate (AIM31) and 4-chloro-2- (4-(trifluoromethyl)phenylcarbamoyl)phenyl acetate (AIM33). Investigation of the chemical structures of these three compounds and comparison with a non-inhibitory salicylanilide compound (i.e. 5,3'-diCl-SAL) illustrated that different combinations of chemical groups at defined positions on the salicylanilide core structure had a marked influence on antistaphylococcal activity. The most effective compound was AIM33 which inhibited staphylococcal growth and displayed an initial MIC value of 3.12 µg ml(-1) and subsequent investigation revealed that an MIC as low as of 0.5 µg ml(-1) was achievable. In this case, the dual presence of a trifluoromethyl group and an acetylated phenolic hydroxyl to the salicylanilide core structure led to greatly enhanced activity.