A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA)

Guo, Yi; Meng, Xianhong; Han, Jing

doi:10.1097/md.0000000000012832

Cited by 26 publications

(16 citation statements)

References 31 publications

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“…BMAP-28 effectively inhibited the growth of pan-drug-resistant Acinetobacterbaumannii (PDRAB) by damaging the cell surface with the rapid killing ability [ 70 ]. In another study, Lynn and co-workers found that the two stereoisomers of BMAP-28, D-BMAP-28, and the retro-inverso form (RI-BMAP-28), were highly effective against promastigotes and the intracellular amastigotes stages of Leishmania life cycles.…”

Section: Bovine Ampsmentioning

confidence: 99%

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Kumar

Ali

Singh

et al. 2020

Veterinary Sciences

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Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system, exhibiting evolutionarily conserved characteristics that are present in practically all forms of life. Recent years have witnessed the emergence of antibiotic-resistant bacteria compounded with a slow discovery rate for new antibiotics that have necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidence that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit the least cytotoxicity to the host and exerts a wide spectrum of biological activity including low resistance among microbes and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to a high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for posterity. In this review, we illustrate the diversity of farm animal-specific AMPs, and their biochemical foundations, mode of action, and prospective application in clinics. Subsequently, we present the data for their systematic classification under the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations of their clinical implementation and envision areas for further advancement.

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Section: Bovine Ampsmentioning

confidence: 99%

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Kumar

Ali

Singh

et al. 2020

Veterinary Sciences

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“…BMAP-28 is a well-known broad-spectrum antimicrobial peptide of cathelicidin family. [47][48][49] In general, it is implicated that the presence of proline in a peptide sequence produces kink, which often leads to its non-lytic activity [50,51] against mammalian cells. However, in the BMAP-28 sequence there are two proline residues; one at 19th and the other at 23rd position.…”

Section: Discussionmentioning

confidence: 99%

Introduction of cell‐selectivity in bovine cathelicidin BMAP‐28 by exchanging heptadic isoleucine with the adjacent proline at a non‐heptadic position

et al. 2020

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Bovine cathelicidin, BMAP-28 exhibits potent antimicrobial activity without any cellselectivity. Considering the role of its C-terminus amino acid residues in its cytotoxic activities, we envisioned to rearrange the amino acids at its C-terminus without altering its composition for designing new cell-selective BMAP-28-analog. Thus an isoleucine residue at 20th position, also an "a" position of its previously identified isoleucine zipper sequence, was exchanged with a proline residue at 19th position. As a result, a remarkable reduction in the hemolytic activity of BMAP-28 toward human red blood cells (hRBCs) was observed without hampering its antibacterial activity in liquid media, and in presence of salts and serum. BMAP-28-analog, BMAP-28M depolarized S. aureus membrane and bacterial membrane-mimetic, PE/PG lipid vesicles similar to BMAP-28 but showed weaker efficacy to depolarize hRBC membrane and mammalian membrane-mimetic, PC/Chol vesicles. Differences in the localization of tryptophan residues of BMAP-28 and BMAP-28M were observed only in PC/Chol vesicles. BMAP-28 induced pores of~3.4 nm diameter onto hRBCs whereas BMAP-28M showed minor perturbation onto these cells. BMAP-28 and BMAP-28M induced the entry of calcein (size,~1 nm) and 4.4 kDa FITC-dextran (size,~2.8 nm) into B. megaterium but not of higher sized fluorescent-dextrans indicating toroidal pore formation onto these bacterial membranes. K E Y W O R D S antimicrobial and hemolytic activity, BMAP-28, cathelicidin antimicrobial peptides, dissipation of diffusion potential across membranes, estimation of peptide-induced pore sizes onto bacteria, mode of action of antimicrobial peptides, osmotic protection assay | INTRODUCTIONThere are mainly two antimicrobial peptide families in the mammalian system viz. Defensins and Cathelicidins. [1,2] Structures of Defensins are generally based on beta-sheet core, stabilized by three disulfide bonds [1][2][3] but cathelicidins are quite diverse. [1,4] By and large, the AMPs of the cathelicidin family are linear in nature comprised of 20 to 40 amino acid (a.a.) residues that adopt an alpha-helical conformation Abbreviations: AMP, antimicrobial peptides; CFU, colony-forming unit; Chol, cholesterol; HPLC, high-performance liquid chromatography; hRBCs, human red blood cells; MALDI-TOF, matrix-assisted laser desorption ionization time of flight; MICs, minimum inhibitory concentrations; PBS, phosphate-buffered saline; PC, phosphatidylcholine; PE, egg phosphatidylethanolamine; PG, egg phosphatidylglycerol.

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“…baumannii by interacting with AbOmpA. These compounds started to destroy A. baumannii at the concentration of 40 μg/mL within only 15 min, and after 30 min, the bacterial cells were obviously damaged with leaking cytoplasm [77]. In addition, LL-37 interacted with the amino acid residues 74-84 of AbOmpA in a dose dependent way, decreasing the adhesion of A. baumannii to host cells.…”

Section: Therapeutic Strategies Targeting Abompa Polypeptidementioning

confidence: 99%

Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

et al. 2020

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Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing serious nosocomial infections, which is considered as the most threatening Gram-negative bacteria (GNB). Outer membrane protein A (OmpA), a major component of outer membrane proteins (OMPs) in GNB, is a key virulence factor which mediates bacterial biofilm formation, eukaryotic cell infection, antibiotic resistance and immunomodulation. The characteristics of OmpA in Escherichia coli (E. coli) have been extensively studied since 1974, but only in recent years researchers started to clarify the functions of OmpA in A. baumannii. In this review, we summarized the structure and functions of OmpA in A. baumannii (AbOmpA), collected novel therapeutic strategies against it for treating A. baumannii infection, and emphasized the feasibility of using AbOmpA as a potential therapeutic target.

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A bovine myeloid antimicrobial peptide (BMAP-28) and its analogs kill pan-drug-resistant Acinetobacter baumannii by interacting with outer membrane protein A (OmpA)

Abstract: Supplemental Digital Content is available in the text

Cited by 26 publications

References 31 publications

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Introduction of cell‐selectivity in bovine cathelicidin BMAP‐28 by exchanging heptadic isoleucine with the adjacent proline at a non‐heptadic position

Outer membrane protein A (OmpA) as a potential therapeutic target for Acinetobacter baumannii infection

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