Value Addition in the Efficacy of Conventional Antibiotics by Nisin against Salmonella

Abstract

Frequent and indiscriminate use of existing battery of antibiotics has led to the development of multi drug resistant (MDR) strains of pathogens. As decreasing the concentration of the antibiotic required to treat Salmonellosis might help in combating the development of resistant strains, the present study was designed to assess the synergistic effects, if any, of nisin, in combination with conventional anti-Salmonella antibiotics against Salmonella enterica serovar Typhimurium. Minimum inhibitory concentrations (MICs) of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by radial diffusion assay, fractional inhibitory concentration (FIC) index (checkerboard test) and time-kill assay. Scanning electron microscopy (SEM) was also performed to substantiate the effect of the combinations. In-vivo synergistic efficacy of the combinations selected on the basis of in-vitro results was also evaluated in the murine model, in terms of reduction in the number of Salmonellae in liver, spleen and intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have additive effects, whereas the combinations of nisin-ceftriaxone and nisin-cefotaxime were found to be highly synergistic against serovar Typhimurium as evident by checkerboard test and time-kill assay. SEM results revealed marked changes on the outer membrane of the bacterial cells treated with various combinations. In-vivo synergy was evident from the larger log unit decreases in all the target organs of mice treated with the combinations than in those treated with drugs alone. This study thus highlights that nisin has the potential to act in conjunction with conventional antibiotics at much lower MICs. These observations seem to be significant, as reducing the therapeutic concentrations of antibiotics may be a valuable strategy for avoiding/reducing the development of emerging antibiotic resistance. Value added potential of nisin in the efficacy of conventional antibiotics may thus be exploited not only against Salmonella but against other Gram-negative infections as well.

Bacteriocins and their position in the next wave of conventional antibiotics

“…It is critical to note that bacteriocins are capable of addressing these routes through distinct mechanisms of action that differ from antibiotics. Septum formation and other associated distinctive targets of cell membrane formation are of particular interest [83]. Other internal targets, such as gene expression and protein production, are also of interest.…”

“…It has been indicated that the combination of nisin with ceftriaxone or with cefotaxime assists in permeating the outer membrane of Salmonella spp. [83]. Membrane permeabilisation from a -lactam antibiotic allows for the uptake of nisin.…”

Co-spinning of Silver Nanoparticles with Nisin Increases the Antimicrobial Spectrum of PDLLA: PEO Nanofibers

“…The lantibiotic, classified as a class I bacteriocin, is active against a number of gram-positive bacteria such as S. aureus, Streptococcus pneumonia, Clostridium difficile, Listeria monocytogenes, Bacillus cereus, and Clostridium botulinum [1,5,10]. Gram-negative bacteria are resistant to nisin, but some examples of growth inhibition were reported when cells were pre-treated with EDTA [17,19]. EDTA chelates Mg 2?…”

Evaluation of nisin–β-lactam antibiotics against clinical strains of Salmonella enterica serovar Typhi

“…7,13 Overnight growth was monitored by measuring the OD at 620 nm. The MIC was defined as the lowest concentration of each antibiotic not producing any visible microbial growth.…”

“…One such example is nisin, a well-known broad spectrum bacteriocin active against Gram-positive pathogens associated with foods. 7 However, it is not active against Gram-negative organisms because the outer membrane (OM) of the Gram-negative cell wall acts as a barrier for the cell, restricting the access of the peptide to the cytoplasmic membrane. 8 Nonetheless, certain agents like EDTA, citrate and plant essential oils which can disrupt the OM of Gram-negative bacteria can render them susceptible to nisin, but its use in clinical trials is restricted due to the limitations on in-vivo use of EDTA.…”