Abstract
With the alarming increase of infections caused by pathogenic multidrug-resistant bacteria over the last decades, antimicrobial peptides (AMPs) have been investigated as a potential treatment for those infections, directly through their lytic effect or indirectly, due to their ability to modulate the immune system. There are still concerns regarding the use of such molecules in the treatment of infections, such as cell toxicity and host factors that lead to peptide inhibition. To overcome these limitations, different approaches like peptide modification to reduce toxicity and peptide combinations to improve therapeutic efficacy are being tested. Human defense peptides consist of an important part of the innate immune system, against a myriad of potential aggressors, which have in turn developed different ways to overcome the AMPs microbicidal activities. Since the antimicrobial activity of AMPs vary between Gram-positive and Gram-negative species, so do the bacterial resistance arsenal. This review discusses the mechanisms exploited by Gram-positive bacteria to circumvent killing by antimicrobial peptides. Specifically, the most clinically relevant genera, Streptococcus spp., Staphylococcus spp., Enterococcus spp. and Gram-positive bacilli, have been explored.
Highlights
Antimicrobial peptides, known as host defense peptides (HDPs), are found in most life forms, being part of the innate immune system against pathogenic bacteria, fungi, parasites and viruses (Zasloff, 2002; Torrent et al, 2012)
The development of antimicrobial resistance against antimicrobial peptides (AMPs) is not as prevalent when compared to antibiotics, since AMPs targets are diverse and changes can interfere with the functionality of the cell, especially since the cell membrane is the main point of attack (Mahlapuu et al, 2016)
A more recent study from the same group, analyzed the transcriptome of the bacterium after exposure to bacitracin. They found 8 genes (SMU.302, SMU.862, SMU.863, SMU.864, mbrA, mbrB, SMU.1479, SMU.1856c) that were upregulated upon AMP challenge; of those, the MbrC protein acts as a transcriptional regulator for MbrA and MbrB–which are part of the ABC transporter and are required for bacitracin resistance–and it controls the expression of SMU.863 and SMU.864, described as ABC transporters involved in bacitracin resistance by S. mutans (Kitagawa et al, 2011)
Summary
Antimicrobial peptides, known as host defense peptides (HDPs), are found in most life forms, being part of the innate immune system against pathogenic bacteria, fungi, parasites and viruses (Zasloff, 2002; Torrent et al, 2012). Indolicidin, a 13 amino acid peptide expressed in bovine neutrophils, has antimicrobial activity against Gram-positive and Gram-negative bacteria (van Harten et al, 2018) Another class of cationic and amphipathic antimicrobial peptides is the defensins, which can be divided in three main groups: α-defensins, β-defensins and θ-defensins. Α-defensins can be found in many different tissues such as the gastrointestinal and respiratory epithelia, female reproductive tract and blood cells (Hancock et al, 2016) These peptides display direct antimicrobial activities and immunomodulatory effects, including chemotaxis (Wang, 2014; Moravej et al, 2018; Xu and Lu, 2020). C. tetani produces the tetanus neurotoxin (TeNT) that causes neurological disease (tetanus), characterized by muscle spasms and spastic
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