Synergy of antimicrobial peptides.

Abstract

Emerging multidrug-resistant organisms challenge the medical community to search for new, effective antimicrobial agents to combat infection. Antimicrobial peptides (AMPs) offer a solution for this challenge and could play a major role in the search for new therapeutic regimens against MDR organisms. These peptides can be utilized in their natural or in synthetic forms, or modulated by agents increasing their natural production in vivo via altered gene regulation. Combinations of AMPs with conventional antibiotics and duplicate and triplicate combinations of AMPs are effective in combating Gram-positive and Gramnegative bacteria, as well as parasites and fungi. AMPs of different classes as well as a common class can be combined to induce synergy, enhancing the antimicrobial activity of each peptide or antibiotic compared with its activity alone. Although some specific triple AMP combinations are more effective than specific double AMP combinations, enhancement is generally not a simple stoichiometric relationship. The synergy between AMPs is complex and depends on the concentration and the combination of specific AMPs. Mechanisms include combining membrane-permeabilizing activities as well as modulating the innate immune system to combat inflammatory activity induced by the microorganisms. Mechanisms of AMP-enhanced antibiotic activity are not well studied, although it is postulated that the membrane altering effects allow for increased permeabilization of the membrane to the antibiotic, enhancing antimicrobial activity. Combinations of AMPs with conventional antibiotics serve the advantage of overcoming microbial resistance to the antibiotic as well as decreasing some of the toxicity of certain antibiotics in the patient. Creation of chemical compounds, termed AMP mimetics, that could replace AMPs known to combine with antibiotics to enhance activity would be advantageous in solving the problem of economically feasible AMP production. The examination of synergy with this new class of antibiotics is needed, for the pharmacodynamics of synergy and antagonism between combinations of these agents is complex and varies with the specific combination of agents. So far, research results demonstrate that synergy between AMPs or their mimetics, between themselves or with existing antibiotics offers a solution to the antibiotic resistance problem.

β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea

“…In human airway epithelial cells, the capsule of Klebsiella pneumoniae protects the bacterium from β-defensin bactericidal action and impedes the expression of mBD-4 and mBD-14, for mutant bacteria lacking the capsule induce higher levels of β-defensin-3, -4 and -14 in vivo than the WT bacteria. In addition, the concept of β-defensins and other antimicrobial peptides working together as therapeutic agents has also been demonstrated [ 49 , 50 ].…”

Predicting Antimicrobial Activity for Untested Peptide-Based Drugs Using Collaborative Filtering and Link Prediction

“…It is expected then that two different types of AMPs complement each other in the pore-opening process. For example, antimicrobial peptides PGLA and magainin-2 are highly synergistic, and their mechanism of action has been proposed to be through complementary functions: PGLA forms pores relatively fast, but these pores are not as stable as those formed by magainin-2 [40]. But together they can form fast and stable membrane pores.…”

Occurrence of Antibiotics and Bacterial Resistance Genes in Wastewater Resistance Mechanisms and Antimicrobial Resistance Control Approaches

“…Antibiotic overuse, inappropriate prescription, and extensive use of antibiotics in agriculture are linked to the widespread occurrence of antibiotics in the environment [6]. These and other anthropogenic activities that result in the discharge of wastewater containing antibiotics and/or their metabolites into environmental matrices have been attributed to the increasing antimicrobial resistance due to the rapid evolution of bacteria facilitated by the acquisition of resistance from the reservoir of ARGs, which has a direct impact on the control of microbial pathogens in humans and animals [12,88].…”

“…More than 50 genes encoding AME have been described, but many variants of the gene cassette-borne acetyltransferases (AAC) appear to dominate in clinically important Gram-negative bacteria [158]. Variants of aminoglycoside modifying enzymes such as AAC1, AAC2, AAC4 and APH (6) have been detected in bacteria isolated from hospital wastewater and in both the influent and effluent of WWTPs [159].…”

“…[4]. However, despite their potential environmental and health effects, the use of these agents has revolutionized www.videleaf.com health care by improving hygiene and considerably changing the outcome of bacterial infections, which has in turn, significantly increased the average expected lifespan [5,6]. Their consumption varies from region to region and from country to country [7].…”