scholarly journals A polyalanine peptide derived from polar fish with anti-infectious activities

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Marlon H. Cardoso ◽  
Suzana M. Ribeiro ◽  
Diego O. Nolasco ◽  
César de la Fuente-Núñez ◽  
Mário R. Felício ◽  
...  

Abstract Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 192 ◽  
Author(s):  
Feng Wang ◽  
Xinyu Ji ◽  
Qiupeng Li ◽  
Guanling Zhang ◽  
Jiani Peng ◽  
...  

New strategies against antibiotic-resistant bacterial pathogens are urgently needed but are not within reach. Here, we present in vitro and in vivo antimicrobial activity of TSPphg, a novel phage lysin identified from extremophilic Thermus phage TSP4 by sequencing its whole genome. By breaking down the bacterial cells, TSPphg is able to cause bacteria destruction and has shown bactericidal activity against both Gram-negative and Gram-positive pathogenic bacteria, especially antibiotic-resistant strains of Klebsiella pneumoniae, in which the complete elimination and highest reduction in bacterial counts by greater than 6 logs were observed upon 50 μg/mL TSPphg treatment at 37 °C for 1 h. A murine skin infection model further confirmed the in vivo efficacy of TSPphg in removing a highly dangerous and multidrug-resistant Staphylococcus aureus from skin damage and in accelerating wound closure. Together, our findings may offer a therapeutic alternative to help fight bacterial infections in the current age of mounting antibiotic resistance, and to shed light on bacteriophage-based strategies to develop novel anti-infectives.


mSphere ◽  
2021 ◽  
Author(s):  
Catrina Olivera ◽  
Murray P. Cox ◽  
Gareth J. Rowlands ◽  
Jasna Rakonjac

Synergistic antibiotic combinations are a promising alternative strategy for developing effective therapies for multidrug-resistant bacterial infections. The synergistic combination of the existing antibiotics nitrofurans and vancomycin with sodium deoxycholate shows promise in inhibiting and killing multidrug-resistant Gram-negative bacteria.


2021 ◽  
Vol 8 ◽  
Author(s):  
Firdoos Ahmad Gogry ◽  
Mohammad Tahir Siddiqui ◽  
Insha Sultan ◽  
Qazi Mohd. Rizwanul Haq

Colistin regained global interest as a consequence of the rising prevalence of multidrug-resistant Gram-negative Enterobacteriaceae. In parallel, colistin-resistant bacteria emerged in response to the unregulated use of this antibiotic. However, some Gram-negative species are intrinsically resistant to colistin activity, such as Neisseria meningitides, Burkholderia species, and Proteus mirabilis. Most identified colistin resistance usually involves modulation of lipid A that decreases or removes early charge-based interaction with colistin through up-regulation of multistep capsular polysaccharide expression. The membrane modifications occur by the addition of cationic phosphoethanolamine (pEtN) or 4-amino-l-arabinose on lipid A that results in decrease in the negative charge on the bacterial surface. Therefore, electrostatic interaction between polycationic colistin and lipopolysaccharide (LPS) is halted. It has been reported that these modifications on the bacterial surface occur due to overexpression of chromosomally mediated two-component system genes (PmrAB and PhoPQ) and mutation in lipid A biosynthesis genes that result in loss of the ability to produce lipid A and consequently LPS chain, thereafter recently identified variants of plasmid-borne genes (mcr-1 to mcr-10). It was hypothesized that mcr genes derived from intrinsically resistant environmental bacteria that carried chromosomal pmrC gene, a part of the pmrCAB operon, code three proteins viz. pEtN response regulator PmrA, sensor kinase protein PmrAB, and phosphotransferase PmrC. These plasmid-borne mcr genes become a serious concern as they assist in the dissemination of colistin resistance to other pathogenic bacteria. This review presents the progress of multiple strategies of colistin resistance mechanisms in bacteria, mainly focusing on surface changes of the outer membrane LPS structure and other resistance genetic determinants. New handier and versatile methods have been discussed for rapid detection of colistin resistance determinants and the latest approaches to revert colistin resistance that include the use of new drugs, drug combinations and inhibitors. Indeed, more investigations are required to identify the exact role of different colistin resistance determinants that will aid in developing new less toxic and potent drugs to treat bacterial infections. Therefore, colistin resistance should be considered a severe medical issue requiring multisectoral research with proper surveillance and suitable monitoring systems to report the dissemination rate of these resistant genes.


2021 ◽  
Author(s):  
Apoorva Vishwakarma ◽  
Francis Dang ◽  
Allison Ferrell ◽  
Hazel A. Barton ◽  
Abraham Joy

Over 80% of all chronic bacterial infections in humans are associated with biofilms, which are surface-associated bacterial communities encased within a secreted exopolysaccharide matrix that can provide resistance to environmental and chemical insults. Biofilm formation triggers broad adaptive changes in the bacteria, allowing them to be almost a thousand-fold more resistant to conventional antibiotic treatments and host immune responses. The failure of antibiotics to eliminate biofilms leads to persistent chronic infections and can promote the development of antibiotic-resistant strains. Therefore, there is an urgent need to develop agents that effectively prevent biofilm formation and eradicate established biofilms. Herein, we present water-soluble synthetic peptidomimetic polyurethanes that can disrupt surface established biofilms of <i>Pseudomonas aeruginosa, Staphylococcus aureus, </i>and <i>Escherichia coli</i>, all of which show tolerance to the conventional antibiotics polymyxin B and ciprofloxacin. Furthermore, these polyurethanes prevent bacterial attachment and stimulate bacterial surface motility to inhibit biofilm formation of both Gram-positive and Gram-negative bacteria at sub-inhibitory concentrations, without being toxic to mammalian cells. Our results show that these polyurethanes show promise as a platform for the development of therapeutics that target biofilms and modulate surface interactions of bacteria for the treatment of chronic biofilm-associated infections and as antibiofilm agents.


2008 ◽  
Vol 21 (4) ◽  
pp. 1013-1020 ◽  
Author(s):  
H. Yadav ◽  
M. Yadav ◽  
S. Jain ◽  
A. Bhardwaj ◽  
V. Singh ◽  
...  

In this study, a herbal preparation containing Dalbergia sissoo and Datura stramoium with cow urine (DSDS), was evaluated for its antibacterial potential against pathogenic strains of gram-positive ( Staphylococcus aureus and Streptococcus pneumoniae) and gram-negative ( Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) bacteria. Antibacterial activity was compared to standard antibiotic drugs i.e. Chloramphenicol (30 mcg), Ampicillin (10 mcg), Nalidixic acid (10 mcg) and Rifampicin (30 mcg). Cow urine extract was found to be most active against both gram-positive as well as gram-negative bacteria. Clinical isolate of S. aureus showed higher sensitivity towards cow urine extract of DSDS than standard strains, and inhibited growth on most regulatory levels such as inhibition of protein, DNA, RNA and peptidoglycan synthesis. The results of the present study shows that the cow urine extract of DSDS may be used as a potent antiseptic preparation for prevention and treatment of chronic bacterial infections.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miao Dong ◽  
Shu Hin Kwok ◽  
Joseph L. Humble ◽  
Yimin Liang ◽  
Sze Wing Tang ◽  
...  

AbstractAntimicrobial peptides (AMPs) have emerged as a promising alternative to small molecule antibiotics. Although AMPs have previously been isolated in many organisms, efforts on the systematic identification of AMPs in fish have been lagging. Here, we collected peptides from the plasma of medaka (Oryzias latipes) fish. By using mass spectrometry, 6399 unique sequences were identified from the isolated peptides, among which 430 peptides were bioinformatically predicted to be potential AMPs. One of them, a thermostable 13-residue peptide named BING, shows a broad-spectrum toxicity against pathogenic bacteria including drug-resistant strains, at concentrations that presented relatively low toxicity to mammalian cell lines and medaka. Proteomic analysis indicated that BING treatment induced a deregulation of periplasmic peptidyl-prolyl isomerases in gram-negative bacteria. We observed that BING reduced the RNA level of cpxR, an upstream regulator of envelope stress responses. cpxR is known to play a crucial role in the development of antimicrobial resistance, including the regulation of genes involved in drug efflux. BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria. In addition, exposure to sublethal doses of BING delayed the development of antibiotic resistance. To our knowledge, BING is the first AMP shown to suppress cpxR expression in Gram-negative bacteria. This discovery highlights the cpxR pathway as a potential antimicrobial target.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eun Young Kim ◽  
So Hee Han ◽  
Jong Min Kim ◽  
Seon-Myung Kim ◽  
Song Yub Shin

AbstractSAMP-5 is a short histidine-derived antimicrobial peptidomimetic with pendant dialkylated tail. In this study, we evaluated the potential of SAMP-5 as an antimicrobial agent to combat multidrug-resistant gram-negative bacteria. SAMP-5 showed potent antimicrobial activity (minimum inhibitory concentration 16-64 μg/ml) comparable to melittin against multidrug-resistant Escherichia coli (MDREC) and multidrug-resistant (MDRPA). SAMP-5 displayed no cytotoxicity against three mammalian cells such as mouse macrophage RAW264.7, mouse embryonic fibroblast NIH-3T3, and human bone marrow SH-SY5Y cells at the concentration of 128 μg/ml. SAMP-5 showed resistance to proteolytic degradation with pepsin, trypsin, α-chymotrypsin, and proteinase K. Importantly, unlike ciprofloxacin, no antibiotic resistance against SAMP-5 arose for Pseudomonas aeruginosa during 7 days of serial passage at 0.5 × MIC. Moreover, SAMP-5 showed synergy or additive effects against MDRPA and MDREC, when it combined with chloramphenicol, ciprofloxacin, and oxacillin. Collectively, our results suggested that SAMP-5 is a promising alternative and adjuvant to treat infections caused by multidrug-resistant gram-negative bacteria.


2021 ◽  
Author(s):  
Apoorva Vishwakarma ◽  
Francis Dang ◽  
Allison Ferrell ◽  
Hazel A. Barton ◽  
Abraham Joy

Over 80% of all chronic bacterial infections in humans are associated with biofilms, which are surface-associated bacterial communities encased within a secreted exopolysaccharide matrix that can provide resistance to environmental and chemical insults. Biofilm formation triggers broad adaptive changes in the bacteria, allowing them to be almost a thousand-fold more resistant to conventional antibiotic treatments and host immune responses. The failure of antibiotics to eliminate biofilms leads to persistent chronic infections and can promote the development of antibiotic-resistant strains. Therefore, there is an urgent need to develop agents that effectively prevent biofilm formation and eradicate established biofilms. Herein, we present water-soluble synthetic peptidomimetic polyurethanes that can disrupt surface established biofilms of <i>Pseudomonas aeruginosa, Staphylococcus aureus, </i>and <i>Escherichia coli</i>, all of which show tolerance to the conventional antibiotics polymyxin B and ciprofloxacin. Furthermore, these polyurethanes prevent bacterial attachment and stimulate bacterial surface motility to inhibit biofilm formation of both Gram-positive and Gram-negative bacteria at sub-inhibitory concentrations, without being toxic to mammalian cells. Our results show that these polyurethanes show promise as a platform for the development of therapeutics that target biofilms and modulate surface interactions of bacteria for the treatment of chronic biofilm-associated infections and as antibiofilm agents.


2021 ◽  
Vol 9 (02) ◽  
pp. 152-159
Author(s):  
Sibabrata Bhattacharya ◽  
◽  
Ankan Chakrabarti ◽  
Tapan Majumdar ◽  
◽  
...  

Background- Secondary bacterial infections including bacteremia have been implicated as a major cause of morbidity and mortality in COVID-19 patients So, it is important to determine the bacteriological profile of organisms responsible for bacteremia among COVID-19 patients along with their antimicrobial resistance pattern Objectives- To determine the bacteriological profile, antimicrobial resistance pattern and clinical outcome among COVID-19 patients with bacteremia as manifestation of secondary bacterial infection. Study design- Single center, cross sectional study Methods- Blood cultures were obtained from COVID-19 patients with features of bacteremia and sepsis based on Sepsis-3 criteria and serum procalcitonin level. Identification and AST were performed and the patients were followed until final outcome or discharge from hospital. Results- Among 43 blood samples obtained. 8 were positive in culture for pathogenic bacteria (18.6%). Mean age of the patients were 53.4 ± 14.9 years with male preponderance (62.5%). Mean procalcitonin level was 6.5±5.7 ng/ml. Positive history of contact was the major risk factor (62.5%) and mean duration of hospital stay was 11.1± 3.9 days. Mortality rate was 37.5%. Gram negative bacilli were the major isolates (75%) and one case was caused by an unusual organism Erysipelothrixrhusiopathiae. Among the Gram negative bacilli, maximum resistance was against Amikacin (100%) and minimum against Meropenem (16.7%). Out of GNB isolates, one isolate of Pseudomonas aeruginosa was Metallo ? lactamase enzyme producer and another one was multidrug resistant strain. Conclusion- Bacteremia among COVID-19 patients is a serious form of bacterial co-infection, leading to increased morbidity and mortality among the patients. High degree of clinical suspicion and increasing prolactin level must be complemented with blood culture to rule out bacteremia in these patients, where timely intervention and proper antimicrobial therapy can be lifesaving. Keywords- COVID-19, SARS-CoV-2, Coronavirus, Bacterial coinfection, Bacteremia, Antimicrobial resistance.


Processes ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1173 ◽  
Author(s):  
Murugesan Chandrasekaran ◽  
Ki Deok Kim ◽  
Se Chul Chun

In recent years, nanotechnology has attracted attention in many fields because it has several up-and-coming novel uses. Many researchers have suggested that chitosan nanoparticles (CS-NPs) and their derivatives are one of the best nanomaterials for delivering antibacterial activity. CS-NPs have a broad spectrum of antibacterial activity, but they manifest different inhibitory efficacy against gram-negative (G−) and gram-positive (G+) bacterial species. The mechanism of antibacterial action is an intricate process that varies between G− and G+ bacteria as a result of the differences in cell wall and cell membrane chemistry. In previous studies, greater antibacterial activity was more evident against G− bacteria than G+ bacteria, whereas in some studies G+ bacteria were more sensitive. Researchers predicted that the varied responses of bacteria are caused by the mixed hydrophilicity and negative charge distribution on the bacterial surface. Moreover, its activity depends on a number of variables including bacterial target (i.e., G− or G+ bacteria) and bacterial growth, as well as its concentration, pH, zeta-potential, molecular weight, and degree of acetylation. Therefore, this review examines current research on the mechanisms and factors affecting antibacterial activity, and application of CS-NPs specifically against animal and plant pathogenic bacteria.


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