5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

2019 ◽  
Author(s):  
Bram Frohock ◽  
Jessica M. Gilbertie ◽  
Jennifer C. Daiker ◽  
Lauren V. Schnabel ◽  
Joshua Pierce
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Matrix Model ◽  
Bacterial Load ◽  
Collagen Matrix ◽  
Resistance Mechanisms ◽  
Novel Therapeutics ◽  
Innovative Treatment ◽  
Antibiotic Action ◽  
Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

5-Benzylidene-4-Oxazolidinones are Synergistic with Antibiotics for the Treatment of Staphylococcus Aureus Biofilms

2019 ◽  
Author(s):  
Bram Frohock ◽  
Jessica M. Gilbertie ◽  
Jennifer C. Daiker ◽  
Lauren V. Schnabel ◽  
Joshua Pierce
Keyword(s):  
Staphylococcus Aureus ◽  
Human Health ◽  
Matrix Model ◽  
Bacterial Load ◽  
Collagen Matrix ◽  
Resistance Mechanisms ◽  
Novel Therapeutics ◽  
Innovative Treatment ◽  
Antibiotic Action ◽  
Biofilm Infection

<div>The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative treatment approaches to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms and in combination with common antibiotics are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.</div>

Emerging Antimicrobial Resistance Among Methicillin Resistant Staphylococcus Aureus (MRSA) in a Tertiary Care Centre in North India

JMS SKIMS ◽  
2020 ◽  
Vol 23 (1) ◽  
pp. 48-49
Author(s):  
Javaid Ahmad Bhat ◽  
Shariq Rashid Masoodi
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Tertiary Care ◽  
Resistance Mechanisms ◽  
North India ◽  
Global Public Health ◽  
Care Centre ◽  
Tertiary Care Centre ◽  
Effective Prevention ◽  
Mupirocin Resistance

Apropos to the article by Dr Bali, titled “Mupirocin resistance in clinical isolates of methicillin-sensitive and resistant Staphylococcus aureus in a tertiary care centre of North India” (1), the authors have raised important issue of emerging antimicrobial resistance (AMR). Antimicrobial resistance is an increasingly serious threat to global public health that requires action across all government sectors and society. As per WHO, AMR lurks the effective prevention and management of an ever-increasing spectrum of infections caused by bacteria, parasites, fungi and viruses. Novel resistance mechanisms are emerging and spreading globally, threatening the man’s ability to treat common infectious diseases.

Effect of antibiotics on the bacterial load of meticillin-resistant Staphylococcus aureus colonisation in anterior nares

2008 ◽  
Vol 70 (1) ◽  
pp. 27-34 ◽  
Author(s):  
V.C.C. Cheng ◽  
I.W.S. Li ◽  
A.K.L. Wu ◽  
B.S.F. Tang ◽  
K.H.L. Ng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Load

scholarly journals Staphylococcus aureus: A Review of Antimicrobial Resistance Mechanisms

2018 ◽  
Vol 4 (2) ◽  
Author(s):  
Asinamai Athliamai Bitrus ◽  
Olabode Mayowa Peter ◽  
Muhammad Adamu Abbas ◽  
Mohammed Dauda Goni
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Resistance Mechanisms

scholarly journals Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – II Infection with Persister Forms of Staphylococcus aureus Causes a Chronic Persistent Skin Infection with More Severe Lesion that Takes Longer to Heal and is not Eradicated by the Current Recommended Treatment in Mice

2018 ◽  
Author(s):  
Rebecca Yee ◽  
Yuting Yuan ◽  
Cory Brayton ◽  
Andreina Tarff Leal ◽  
Jie Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Stationary Phase ◽  
Skin Infection ◽  
Bacterial Load ◽  
Mouse Skin ◽  
Infection Model ◽  
Persister Cells ◽  
Persistent Infections ◽  
Recommended Treatment ◽  
Biofilm Bacteria

AbstractStaphylococcus aureus is an opportunistic pathogen that can cause persistent infections clinically. Treatment for chronic S. aureus infections ranges from at least one week to several months and such infections are prone to relapse likely due to the presence of persistent forms of bacteria such as persister cells. Persister cells, which are bacterial cells that become dormant under stress conditions, can be isolated in vitro but their clinical significance in in vivo infections are largely unclear. Here, we evaluated S. aureus persistent forms using stationary phase cultures and biofilm bacteria (enriched in persisters) in comparison with log phase cultures in terms of their ability to cause disease in a mouse skin infection model. Surprisingly, we found that infection of mice with stationary phase cultures and biofilm bacteria produced a more severe chronic skin infection with more pronounced lesions which took longer to heal than log phase (actively growing) cultures. After two week infection, the bacterial load and skin tissue pathology, as determined by hyperplasia, immune cell infiltration, and crust/lesion formation, of mice infected with the more persistent forms (e.g. stationary phase bacteria and biofilm bacteria) were greater than mice infected with log phase bacteria. Using our persistent infection mouse model, we showed that the clinically recommended treatment for recurrent S. aureus skin infection, doxycycline + rifampin, was not effective in eradicating the bacteria in the treatment study, despite reducing lesion sizes and pathology in infected mice. Analogous findings were also observed in a Caenorhabditis elegans model, where S.aureus stationary phase cultures caused a greater mortality than log phase culture as early as two days post-infection. Thus, we established a new model for chronic persistent infections using persister bacteria that could serve as a relevant model to evaluate therapeutic options for persistent infections in general. Our findings connect persisters with persistent infections, have implications for understanding disease pathogenesis, and are likely to be broadly valid for other pathogens.

scholarly journals Genomic investigation of Staphylococcus aureus recovered from Gambian women and newborns following an oral dose of intra-partum azithromycin

2019 ◽  
Vol 74 (11) ◽  
pp. 3170-3178
Author(s):  
Abdoulie Bojang ◽  
Sarah L Baines ◽  
Liam Donovan ◽  
Romain Guerillot ◽  
Kerrie Stevens ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Epidemiological Data ◽  
Resistance Mechanisms ◽  
Post Intervention ◽  
Main Trial ◽  
Long Read ◽  
Macrolide Resistance Gene ◽  
Genome Analyses ◽  
Study Participants

Abstract Background Oral azithromycin given during labour reduces carriage of bacteria responsible for neonatal sepsis, including Staphylococcus aureus. However, there is concern that this may promote drug resistance. Objectives Here, we combine genomic and epidemiological data on S. aureus isolated from mothers and babies in a randomized intra-partum azithromycin trial (PregnAnZI) to describe bacterial population dynamics and resistance mechanisms. Methods Participants from both arms of the trial, who carried S. aureus in day 3 and day 28 samples post-intervention, were included. Sixty-six S. aureus isolates (from 7 mothers and 10 babies) underwent comparative genome analyses and the data were then combined with epidemiological data. Trial registration (main trial): ClinicalTrials.gov Identifier NCT01800942. Results Seven S. aureus STs were identified, with ST5 dominant (n = 40, 61.0%), followed by ST15 (n = 11, 17.0%). ST5 predominated in the placebo arm (73.0% versus 49.0%, P = 0.039) and ST15 in the azithromycin arm (27.0% versus 6.0%, P = 0.022). In azithromycin-resistant isolates, msr(A) was the main macrolide resistance gene (n = 36, 80%). Ten study participants, from both trial arms, acquired azithromycin-resistant S. aureus after initially harbouring a susceptible isolate. In nine (90%) of these cases, the acquired clone was an msr(A)-containing ST5 S. aureus. Long-read sequencing demonstrated that in ST5, msr(A) was found on an MDR plasmid. Conclusions Our data reveal in this Gambian population the presence of a dominant clone of S. aureus harbouring plasmid-encoded azithromycin resistance, which was acquired by participants in both arms of the study. Understanding these resistance dynamics is crucial to defining the public health drug resistance impacts of azithromycin prophylaxis given during labour in Africa.

scholarly journals Summary of Linezolid Activity and Resistance Mechanisms Detected during the 2012 LEADER Surveillance Program for the United States

2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
The United States ◽  
Resistance Mechanisms ◽  
Regulatory Approval ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.

Elimination of Staphylococcus aureus from the bloodstream using a novel biomimetic sorbent haemoperfusion device

2020 ◽  
Vol 13 (8) ◽  
pp. e235262
Author(s):  
Malin-Theres Seffer ◽  
Gabriele Eden ◽  
Susanne Engelmann ◽  
Jan T Kielstein
Keyword(s):  
Staphylococcus Aureus ◽  
Haemodialysis Patient ◽  
Bacterial Load ◽  
Ultrahigh Molecular Weight Polyethylene ◽  
Blood Stream ◽  
Chronic Haemodialysis ◽  
The European Union ◽  
Blood Filter ◽  
First Case ◽  
Ultrahigh Molecular Weight

Removal of bacteria from the blood by means of extracorporeal techniques has been attempted for decades. In late 2019, the European Union licensed the first ever haemoperfusion device for removal of bacteria from the blood. The active ingredient of Seraph 100 Microbind Affinity Blood Filter is ultrahigh molecular weight polyethylene beads with endpoint-attached heparin. Bacteria have been shown to bind to heparin as they would usually do to the heparan sulfate on the cell surface, thereby being removed from the blood stream. We describe the first case of a female chronic haemodialysis patient in which this device was clinically used for a Staphylococcus aureus infection that persisted for 4 days despite antibiotic therapy. After a single treatment, the bacterial load decreased and the blood cultures at the end of a 4 hour haemoperfusion exhibited no bacterial growth.

scholarly journals The Principles, Mechanisms, and Benefits of Unconventional Agents in the Treatment of Biofilm Infection

2020 ◽  
Vol 13 (10) ◽  
pp. 299
Author(s):  
Jasminka Talapko ◽  
Ivana Škrlec
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Treatment Strategies ◽  
Cationic Peptides ◽  
Bacterial Cells ◽  
Infectious Agents ◽  
Severe Infections ◽  
Eskape Pathogens ◽  
Interdependent Relationships ◽  
Biofilm Infection

Today, researchers are looking at new ways to treat severe infections caused by resistance to standard antibiotic therapy. This is quite challenging due to the complex and interdependent relationships involved: the cause of infection–the patient–antimicrobial agents. The sessile biofilm form is essential in research to reduce resistance to very severe infections (such as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanni, Pseudomonas aeruginosa, and Enterobacter spp). The purpose of this study is to elucidate the mechanisms of the occurrence, maintenance, and suppression of biofilm infections. One form of biofilm suppression is the efficient action of natural antagonists of bacteria—bacteriophages. Bacteriophages effectively penetrate the biofilm’s causative cells. They infect those bacterial cells and either destroy them or prevent the infection spreading. In this process, bacteriophages are specific, relatively easy to apply, and harmless to the patient. Antimicrobial peptides (AMPs) support the mechanisms of bacteriophages’ action. AMPs could also attack and destroy infectious agents on their own (even on biofilm). AMPs are simple, universal peptide molecules, mainly cationic peptides. Additional AMP research could help develop even more effective treatments of biofilm (bacteriophages, antibiotics, AMPs, nanoparticles). Here, we review recent unconventional agents, such as bacteriophages and AMPs, used for eradication of biofilm, providing an overview of potentially new biofilm treatment strategies.

scholarly journals Advanced Resistance Studies Identify Two Discrete Mechanisms in Staphylococcus aureus to Overcome Antibacterial Compounds that Target Biotin Protein Ligase

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 165 ◽  
Author(s):  
Andrew J. Hayes ◽  
Jiulia Satiaputra ◽  
Louise M. Sternicki ◽  
Ashleigh S. Paparella ◽  
Zikai Feng ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Resistance Mechanism ◽  
Resistance Mechanisms ◽  
Resistance Rate ◽  
Biotin Protein Ligase ◽  
Essential Enzyme

Biotin protein ligase (BPL) inhibitors are a novel class of antibacterial that target clinically important methicillin-resistant Staphylococcus aureus (S. aureus). In S. aureus, BPL is a bifunctional protein responsible for enzymatic biotinylation of two biotin-dependent enzymes, as well as serving as a transcriptional repressor that controls biotin synthesis and import. In this report, we investigate the mechanisms of action and resistance for a potent anti-BPL, an antibacterial compound, biotinyl-acylsulfamide adenosine (BASA). We show that BASA acts by both inhibiting the enzymatic activity of BPL in vitro, as well as functioning as a transcription co-repressor. A low spontaneous resistance rate was measured for the compound (<10−9) and whole-genome sequencing of strains evolved during serial passaging in the presence of BASA identified two discrete resistance mechanisms. In the first, deletion of the biotin-dependent enzyme pyruvate carboxylase is proposed to prioritize the utilization of bioavailable biotin for the essential enzyme acetyl-CoA carboxylase. In the second, a D200E missense mutation in BPL reduced DNA binding in vitro and transcriptional repression in vivo. We propose that this second resistance mechanism promotes bioavailability of biotin by derepressing its synthesis and import, such that free biotin may outcompete the inhibitor for binding BPL. This study provides new insights into the molecular mechanisms governing antibacterial activity and resistance of BPL inhibitors in S. aureus.

Sign in / Sign up

Export Citation Format

Share Document