Short antimicrobial peptidomimetic SAMP-5 effective against multidrug-resistant gram-negative bacteria

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.

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Correlated Transcriptional Responses Provide Insights into the Synergy Mechanisms of the Furazolidone, Vancomycin, and Sodium Deoxycholate Triple Combination in Escherichia coli

mSphere ◽

10.1128/msphere.00627-21 ◽

2021 ◽

Author(s):

Catrina Olivera ◽

Murray P. Cox ◽

Gareth J. Rowlands ◽

Jasna Rakonjac

Keyword(s):

Escherichia Coli ◽

Bacterial Infections ◽

Sodium Deoxycholate ◽

Multidrug Resistant ◽

Alternative Strategy ◽

Gram Negative Bacteria ◽

Triple Combination ◽

Transcriptional Responses ◽

Promising Alternative ◽

Gram Negative

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.

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Identification of Ly2 members as antimicrobial peptides from zebrafish Danio rerio

Bioscience Reports ◽

10.1042/bsr20160265 ◽

2017 ◽

Vol 37 (1) ◽

Cited By ~ 6

Author(s):

Xuemin Liu ◽

Xuwen Cao ◽

Su Wang ◽

Guangdong Ji ◽

Shicui Zhang ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Recombinant Proteins ◽

Mammalian Cells ◽

Multidrug Resistant ◽

Scatchard Analysis ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

E Coli ◽

Gram Positive Bacteria

The emergence of multidrug-resistant (MDR) microbes caused by overuse of antibiotics leads to urgent demands for novel antibiotics exploration. Our recent data showed that Ly2.1–3 (a novel lymphocyte antigen 6 (Ly6) gene cluster) were proteins with cationic nature and rich in cysteine content, that are characteristic of antimicrobial peptides (AMPs) and their expression were all significantly up-regulated after challenge with lipopolysaccharide (LPS). These strongly suggested that Ly2.1–3 are potential AMPs, but firm evidence are lacking. Here, we clearly showed that the recombinant proteins of Ly2.1–3 were capable of killing Gram-negative bacteria Aeromonas hydrophila and Escherichia coli, while they had little bactericidal activity against the Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis. We also showed that recombinant proteins Ly2.1–3 (rLy2.1–3) were able to bind to the Gram-negative bacteria A. hydrophila, E. coli and the microbial signature molecule LPS, but not to the Gram-positive bacteria S. aureus and B. subtilis as well as the microbial signature molecule LTA. Moreover, the Scatchard analysis revealed that rLy2.1–3 could specifically bind to LPS. Finally, we found that Ly2.1–3 were not cytotoxic to mammalian cells. All these together indicate that Ly2.1–3 can function as AMPs.

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A novel chemical biology and computational approach to expedite the discovery of new-generation polymyxins against life-threatening Acinetobacter baumannii

Chemical Science ◽

10.1039/d1sc03460j ◽

2021 ◽

Author(s):

Xukai Jiang ◽

Nitin A. Patil ◽

Mohammad A. K. Azad ◽

Hasini Wickremasinghe ◽

Heidi Yu ◽

...

Keyword(s):

Public Health ◽

Chemical Biology ◽

Multidrug Resistant ◽

Computational Approach ◽

Gram Negative Bacteria ◽

Global Public Health ◽

Gram Negative ◽

Life Threatening ◽

New Generation ◽

Novel Antibiotics

Multidrug-resistant Gram-negative bacteria have been an urgent threat to global public health. Novel antibiotics are desperately needed to combat these 'superbugs'.

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Outcomes and Risk Factors in Prosthetic Joint Infections by multidrug-resistant Gram-negative Bacteria: A Retrospective Cohort Study

Antibiotics ◽

10.3390/antibiotics10030340 ◽

2021 ◽

Vol 10 (3) ◽

pp. 340

Author(s):

Raquel Bandeira da Silva ◽

Mauro José Salles

Keyword(s):

Risk Factors ◽

Treatment Failure ◽

Treatment Outcomes ◽

Revision Arthroplasty ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Postoperative Hematoma ◽

Prosthetic Joint ◽

Prosthetic Joint Infections

Gram-negative bacteria (GNB), including multidrug-resistant (MDR) pathogens, are gaining importance in the aetiology of prosthetic joint infection (PJI). This retrospective observational study identified independent risk factors (RFs) associated with MDR-GNB PJI and their influence on treatment outcomes. We assessed MDR bacteria causing hip and knee PJIs diagnosed at a Brazilian tertiary hospital from January 2014 to July 2018. RFs associated with MDR-GNB PJI were estimated by bivariate and multivariate analyses using prevalence ratios (PRs) with significance at p < 0.05. Kaplan–Meier analysis was performed to evaluate treatment outcomes. Overall, 98 PJI patients were analysed, including 56 with MDR-GNB and 42 with other bacteria. Independent RFs associated with MDR-GNB PJI were revision arthroplasty (p = 0.002), postoperative hematoma (p < 0.001), previous orthopaedic infection (p = 0.002) and early infection (p = 0.001). Extensively drug-resistant GNB (p = 0.044) and comorbidities (p = 0.044) were independently associated with MDR-GNB PJI treatment failure. In sum, MDR-GNB PJI was independently associated with previous orthopaedic surgery, postoperative local complications and pre-existing infections and was possibly related to selective pressure on bacterial skin colonisation by antibiotics prescribed for early PJI. Infections due to MDR-GNB and comorbidities were associated with higher treatment failure rates.

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Newer Quinolones in the Treatment of Continuous Ambulatory Peritoneal Dialysis (CAPD) Related Infections

Peritoneal Dialysis International ◽

10.1177/089686089001000202 ◽

1990 ◽

Vol 10 (2) ◽

pp. 127-133 ◽

Cited By ~ 10

Author(s):

Paul Nikolaidis

Keyword(s):

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Adverse Reactions ◽

Antimicrobial Agents ◽

Hospital Staff ◽

Gram Negative Bacteria ◽

Promising Alternative ◽

Gram Negative ◽

Dosing Intervals ◽

Good Oral Bioavailability

Newer fluoroquinolones such as ciprofloxacin, pefloxacin, ofloxacin, enoxacin, and fleroxacin are potent antimicrobial agents against many gram-negative bacteria, including Pseudomonas aeruginosa species and staphylococci-sensitive or resistant to methicillin. They are almost completely absorbed when given orally, reaching therapeutic plasma and dialysate concentrations, and their long half lives permit infrequent dosing intervals. Clinical studies on fluoroquinolones efficacy in continuous ambulatory peritoneal dialysis (CAPD) infections, although not extensive, demonstrate good results. They are well tolerated and the adverse reactions, consisting mainly of gastrointestinal disturbance, were uncommon, mild, and reversible. The fluoroquinolones offer a promising alternative to standard parenteral treatments in CAPD patients, while their good oral bioavailability makes them attractive and convenient for both patients and hospital staff. However, they must be used with caution until we have more information and gain further experience.

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OMN6 a novel bioengineered peptide for the treatment of multidrug resistant Gram negative bacteria

Scientific Reports ◽

10.1038/s41598-021-86155-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shira Mandel ◽

Janna Michaeli ◽

Noa Nur ◽

Isabelle Erbetti ◽

Jonathan Zazoun ◽

...

Keyword(s):

Mechanism Of Action ◽

Antimicrobial Agents ◽

Cyclic Peptide ◽

Safety Margin ◽

Multidrug Resistant ◽

Gram Negative Bacteria ◽

Antibiotic Resistant ◽

Gram Negative ◽

Development Of Resistance ◽

Cecropin A

AbstractNew antimicrobial agents are urgently needed, especially to eliminate multidrug resistant Gram-negative bacteria that stand for most antibiotic-resistant threats. In the following study, we present superior properties of an engineered antimicrobial peptide, OMN6, a 40-amino acid cyclic peptide based on Cecropin A, that presents high efficacy against Gram-negative bacteria with a bactericidal mechanism of action. The target of OMN6 is assumed to be the bacterial membrane in contrast to small molecule-based agents which bind to a specific enzyme or bacterial site. Moreover, OMN6 mechanism of action is effective on Acinetobacter baumannii laboratory strains and clinical isolates, regardless of the bacteria genotype or resistance-phenotype, thus, is by orders-of-magnitude, less likely for mutation-driven development of resistance, recrudescence, or tolerance. OMN6 displays an increase in stability and a significant decrease in proteolytic degradation with full safety margin on erythrocytes and HEK293T cells. Taken together, these results strongly suggest that OMN6 is an efficient, stable, and non-toxic novel antimicrobial agent with the potential to become a therapy for humans.

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832. Assessment of Risk Factors Associated with Wide-resistance Gram-negative Bacteria Infections

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1021 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S457-S457

Author(s):

Henry Pablo Lopes Campos e Reis ◽

Ana Beatriz Ferreira Rodrigues ◽

Julio César Castro Silva ◽

Lia Pinheiro de Lima ◽

Talita Lima Quinaher ◽

...

Keyword(s):

Risk Factors ◽

Mechanical Ventilation ◽

Univariate Analysis ◽

Multidrug Resistant ◽

University Hospital ◽

Gram Negative Bacteria ◽

Multiresistant Pathogens ◽

Gram Negative ◽

Contact Isolation ◽

Bladder Catheter

Abstract Background Enterobacteria and multidrug-resistant non-fermenting Gram-negative bacilli present a challenge in the management of invasive infections, leading to mortality rates due to their limited therapeutic arsenal. The objective of this work was to analyze risk factors that may be associated with these infections, for a better situational mapping and assertive decision-making in a university hospital in Brazil. Methods The study was conducted between January and September 2019, with 167 patients in contact isolation at a university hospital in Brazil. Potential outcome-related variables for wide-resistance Gram-negative bacteria (BGN) infections were evaluated. Risk factors were identified from univariate statistical analysis using Fisher’s test. Results 51 (30.5%) out of 167 patients in contact isolation evolved with wide-resistance BGN infection. Risk factors in univariate analysis were age, hospital unit and previous use of invasive devices. Patients aged up to 59 years were more likely to progress to infection than those aged over 60 years (p 0.0274, OR 2.2, 95% CI 1.1-4.5). Those admitted to the oncohematology (p < 0.001, OR 32.5, Cl 9.1-116.3) and intensive care unit (p < 0.001, OR 28.0, Cl 3.5-225.9) units were more likely to develop this type of infection. The least likely were those admitted to a kidney transplant unit (p 0.0034, OR 15.33, Cl 1.8-131.0). Prior use of mechanical ventilation (p 0.0058, OR 12.2, Cl 2.0-76.1) and delayed bladder catheter (p 0.0266, OR 5.0, Cl 1.2-20.1) in patients with respiratory and urinary tract infection, respectively, were also reported as risk factors related to these infections. The gender of the patients was not significant for the study. Conclusion This study determined that variables such as age, hospitalization unit, use of mechanical ventilation and delayed bladder catheter could be considered important risk factors in triggering the infectious process by wide-resistant gram-negative bacteria. Thus, the analysis of these factors becomes a great foundation to prevent the development of multiresistant pathogens through prevention strategies, prophylaxis management and more targeted empirical therapies. Disclosures All Authors: No reported disclosures

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