Antibacterial efficacy of nisin against multidrug-resistant Gram- positive pathogens

Abstract

The rapid spread of multidrug-resistant bacterial pathogens necessitates the search for alternative antibacterial agents. We examined the efficacy of the antibiotic nisin against 56 multidrug-resistant isolates of Streptococcus pneumoniae, 33 Staphylococcus aureus and 29 vancomycin-resistant Enterococcus faecium and Enterococcus faecalis isolates. The test strains represented a large variety of clonal types (as determined by a combination of DNA fingerprints) isolated from a variety of geographic sources, and included some of the major internationally-spread multiresistant epidemic clones of S. pneumoniae and methicillin-resistant S. aureus (MRSA), MRSA strains resistant to over 16 generically distinct antibacterial agents, and enterococcal strains resistant to all currently available chemotherapeutic agents including glycopeptides. In the overwhelming majority of cases, treatment of growing cultures with nisin at 1 mg/L (S. pneumoniae) or 10-20 mg/L (in MRSA and enterococci) caused extensive (10(3)- to 10(4)-fold) loss of viable titre accompanied by various degrees of loss in the optical density of the cultures, which was most extensive in pneumococci (>90%) and least extensive (40-50%) in enterococci. Nevertheless, extensive variation in rates of nisin-induced autolysis was observed in each bacterial species. Serial exposure of a penicillin-susceptible strain of S. pneumoniae to nisin (1 mg/L) in liquid culture resulted in the rapid appearance of stable nisin-resistant mutants in which the MIC increased from 0.4 to 6.4 mg/L and the resistance trait was transferable by genetic transformation.

The Autolysin LytA Contributes to Efficient Bacteriophage Progeny Release in Streptococcus pneumoniae

“…As a control for cell death, we used the antimicrobial agent nisin, which, by inserting into the cytoplasmic membrane, causes irreparable membrane damage and triggers pneumococcal LytA activity (Fig. 3A) (45). After 10 min, before complete lysis occurred in the wild-type culture, the untreated and the nisin-treated cells formed two well-defined and distinct populations (Fig.…”

Antibacterial Activities of Nisin Z Encapsulated in Liposomes or Produced In Situ by Mixed Culture during Cheddar Cheese Ripening

“…However, several in vivo observations remain enigmatic. For example, the striking differences in sensitivity often observed among different strains of the same bacterial species (55) have not yet been explained, and cell membrane composition seems to play a crucial role in this respect (15,44,52,57,61). The association of nisin with the cell membrane is largely dependent on the type of lipids present and especially on their charge (43).…”

The Expanding Role of Lipid II as a Target for Lantibiotics

“…Detailed descriptions pertaining to the activity spectra and therapeutic potential of lantibiotics have been previously described [39,[44][45][46][47][48].…”

“…It has been shown that many nisin-sensitive Grampositive bacteria, including clinically relevant strains, can acquire nisin resistance upon repeated exposure to increasing nisin concentrations [10,44,94,95]. This type of resistance is often lost once nisin pressure is removed [10] and is more accurately described as a physiological adaptation, although the nisin resistance of Streptococcus bovis was claimed to be stable, resistant cells were rapidly overgrown by sensitive ones [94].…”