Efficacy of Cryptdin-2 as an Adjunct to Antibiotics from Various Generations Against Salmonella

Abstract

Emerging drug resistance in Salmonella coupled with the recent poor success rate of antibiotic discovery programs of the pharmaceutical industry is a cause for significant concern. It has forced the scientific community to look for alternative new classes of antimicrobial compounds. In this context, combinations of antimicrobial peptides (AMPs) and conventional antibiotics have gained interest owing to their versatile applications. The present study was therefore planned to evaluate the synergistic effects, if any, of cryptdin-2, a mouse Paneth cell alphadefensin, in combination with four different antibiotics i.e. ciprofloxacin, ceftriaxone, cefotaxime and chloramphenicol, which are conventionally used against Salmonella. Minimum bactericidal concentrations of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by fractional bactericidal concentration index (checkerboard test) and time-kill assay. Cryptdin-2-ciprofloxacin, cryptdin-2-ceftriaxone and cryptdin-2-cefotaxime combinations were found synergistic as evident by in vitro assays. This synergism provides an additional therapeutic choice by allowing the use of conventional antibiotics in conjunction with AMPs against MDR Salmonella.

Synergism in dual functionality of cryptdin-2 in conjunction with antibiotics against Salmonella

“…Interestingly, β-lactamases are not effective against higher generation cephalosporins with an oxyimino side chain such as cefotaxime, ceftazidime, ceftriaxone, or cefepime9. In our previous study, cryptdin-2 was found to have the potential to augment the activity of conventional, second and third generation anti- Salmonella antibiotics, which was evident by in vitro assays10. In continuation to this, here, we report in vivo synergism in dual functionality i.e.…”

Antimicrobial Activity of Protein Fraction from Naja ashei Venom against Staphylococcus epidermidis

“…In other cases, the second component somehow strengthens the action of the first component by facilitating access to the molecular target. This is how antibacterial peptides work, which cause permeabilization of the membrane, which in turn causes the release of antibiotics into the periplasm and cytoplasm of bacterial cells [42,[51][52][53][54][55][56]. It is also known that Staphylococci have an efflux pump, which determines drug resistance to a large extent because it is responsible for removing from cells various types of substances, which are unnecessary for metabolism or harmful to cells [57].…”

Cryptdin-2 predicts intestinal injury during heatstroke in mice

“…Cryptdins mediate enteric innate immunity, and their absence may contribute to enhanced susceptibility to infection ( 7 , 40 ). Cry-2 can combat infections and augment the activity of conventional antibiotics in vitro and in vivo ( 8 , 9 ). α-defensins may suppress inflammation by controlling the production of interleukin-1β (IL-1β) ( 11 ).…”

“…Increasing evidence suggests that paneth cells, which are found in the small intestines of mammals, are involved in the mucosal barrier function ( 6 ) by secreting apical granules containing antimicrobial peptides, including α-defensins, which are termed cryptdins in mice ( 7 ). Cry-2 has potent antimicrobial activity against certain microbes, including Escherichia coli and Salmonella typhimurium ( 8 , 9 ). Previous results suggest that luminal bacteria can increase the expression of Cry-2, particularly in the ileum ( 10 ).…”