Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations

2020 ◽  
Author(s):  
Colin Hemez ◽  
Fabrizio Clarelli ◽  
Adam C. Palmer ◽  
Leonid Chindelevitch ◽  
Theodore Cohen ◽  
...  
Keyword(s):  
New Drugs ◽  
Resistant Bacteria ◽  
Resistance Mutations ◽  
Antibiotic Resistant ◽  
Resistance Selection ◽  
Drug Mechanism ◽  
Selection Window ◽  
Drug Doses ◽  
Target Binding ◽  
Emergence Of Resistance

AbstractAntibiotic-resistant pathogens are a major public health threat. Understanding how an antibiotic’s mechanism of action influences the emergence of resistance could help to improve the design of new drugs and to preserve the effectiveness of existing ones. To this end, we developed a model that links bacterial population dynamics with antibiotic-target binding kinetics. Our approach allows us to derive mechanistic insights on drug activity from population-scale experimental data and to quantify the interplay between drug mechanism and resistance selection. We find that whether a drug acts as a bacteriostatic or bactericidal agent has little influence on resistance selection. We also show that heterogeneous drug-target binding within a population enables antibiotic-resistant bacteria to evolve secondary mutations, even when drug doses remain above the resistant strain’s minimum inhibitory concentration. Our work suggests that antibiotic doses beyond this “secondary mutation selection window” could safeguard against the emergence of high-fitness resistant strains during treatment.

scholarly journals Antioxidant and Antibacterial Properties of Extracts and Bioactive Compounds in Bryophytes

2021 ◽  
Vol 12 (1) ◽  
pp. 160
Author(s):  
Piergiorgio Cianciullo ◽  
Viviana Maresca ◽  
Sergio Sorbo ◽  
Adriana Basile
Keyword(s):  
Oxidative Stress ◽  
Antibacterial Properties ◽  
Natural Antioxidants ◽  
Antibacterial Activities ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Isolation And Characterization ◽  
State Of Research

Today global health problems such as increased risks of oxidative stress-related diseases and antibiotic resistance are issues of serious concern. Oxidative stress is considered to be the underlying cause of many contemporary pathological conditions such as neurological disorders, ischemia, cancer, etc. Antibiotic-resistant bacteria are a concerning issue in clinical practice, causing an increase in deadly infections. Bryophytes synthesize an outstanding number of secondary metabolites that have shown several potential therapeutic and nutraceutical applications. Research in the field has led to the isolation and characterization of several compounds (flavonoids, terpenoids, and bibenzyls). Some of these compounds have shown promising in vitro antibacterial activities and antioxidant potential comparable to known natural antioxidants such as ascorbic acid and α-tocopherol. However, the process of developing new drugs from naturally occurring molecules is often an impervious path. In this paper, the current state of research of bryophytic antioxidant and antibacterial applications is discussed.

scholarly journals Predictable Phenotypes of Antibiotic Resistance Mutations

mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
M. Knopp ◽  
D. I. Andersson
Keyword(s):  
Antibiotic Resistance ◽  
Resistant Bacteria ◽  
Resistance Mutations ◽  
Resistance Level ◽  
Epistatic Interactions ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Evolutionary Success ◽  
Antibiotic Resistance Mutations ◽  
Host Strains

ABSTRACTAntibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains ofSalmonella entericaandEscherichia colito address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions between different resistance mutations are often predictable from the characteristics of the individual mutations.IMPORTANCEThe spread of antibiotic-resistant bacteria imposes an urgent threat to public health. The ability to forecast the evolutionary success of resistant mutants would help to combat dissemination of antibiotic resistance. Previous studies have shown that the phenotypic effects (fitness and resistance level) of resistance mutations can vary substantially depending on the genetic context in which they occur. We conducted a broad screen using many different resistance mutations and host strains to identify potential epistatic interactions between various types of resistance mutations and to determine the effect of strain background on resistance phenotypes. Combinations of several different mutations showed a large amount of phenotypic predictability, and the majority of the mutations displayed strain-independent phenotypes. However, we also identified a few outliers from these patterns, illustrating that the choice of host organism can be critically important when studying antibiotic resistance mutations.

scholarly journals Anti-Biofilm Activity of the Fungal Phytotoxin Sphaeropsidin A against Clinical Isolates of Antibiotic-Resistant Bacteria

Toxins ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 444
Author(s):  
Emanuela Roscetto ◽  
Marco Masi ◽  
Matilde Esposito ◽  
Roberta Di Lecce ◽  
Antonella Delicato ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Antimicrobial Properties ◽  
Pathogenic Fungi ◽  
Human Infection ◽  
New Drugs ◽  
Clinical Isolates ◽  
Resistant Bacteria ◽  
Clinical Test ◽  
Antibiotic Resistant ◽  
Sphaeropsidin A

Many pathogens involved in human infection have rapidly increased their antibiotic resistance, reducing the effectiveness of therapies in recent decades. Most of them can form biofilms and effective drugs are not available to treat these formations. Natural products could represent an efficient solution in discovering and developing new drugs to overcome antimicrobial resistance and treat biofilm-related infections. In this study, 20 secondary metabolites produced by pathogenic fungi of forest plants and belonging to diverse classes of naturally occurring compounds were evaluated for the first time against clinical isolates of antibiotic-resistant Gram-negative and Gram-positive bacteria. epi-Epoformin, sphaeropsidone, and sphaeropsidin A showed antimicrobial activity on all test strains. In particular, sphaeropsidin A was effective at low concentrations with Minimum Inhibitory Concentration (MIC) values ranging from 6.25 μg/mL to 12.5 μg/mL against all reference and clinical test strains. Furthermore, sphaeropsidin A at sub-inhibitory concentrations decreased methicillin-resistant S. aureus (MRSA) and P. aeruginosa biofilm formation, as quantified by crystal violet staining. Interestingly, mixtures of sphaeropsidin A and epi-epoformin have shown antimicrobial synergistic effects with a concomitant reduction of cytotoxicity against human immortalized keratinocytes. Our data show that sphaeropsidin A and epi-epoformin possess promising antimicrobial properties.

scholarly journals Highlights on the alternatives to antibiotic therapy against bacterial infection

2021 ◽  
Vol 11 (2) ◽  
pp. 194-203
Author(s):  
Bijayanta Sircar ◽  
Shyamapada Mandal
Keyword(s):  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Scientific Data ◽  
New Drugs ◽  
Health Concern ◽  
Antibiotic Resistant ◽  
Effective Drugs ◽  
Emergence Of Resistance ◽  
Antibacterial Capacity

The antibiotic resistance among gram-positive and gram-negative pathogenic bacteria is of global health concern. This has prompted the development of new effective drugs. But the discovery and development of new drugs is slow, and the emergence of resistance to such new drugs, on the other hand, is rapid as well as continuous among the bacteria. Therefore, in tackling the emergence of antibiotic resistant pathogenic bacteria finding alternative ways is vital. This communication, based on the published scientific data, summarizes the antibacterial capacity of some naturally derived agents such as honey, phytocomponents, probiotics, and antimicrobial peptides that might bring new essence in biomedicine.  Keywords: Bacterial resistance, alternative therapeutics, honey, phytomedicine, probiotics, antimicrobial peptides.

Relationship of antibiotic resistance to results of treatment in sepsis patients in Hue Central Hospital 2017 – 2018

2019 ◽  
pp. 48-54
Author(s):  
Duy Binh Nguyen ◽  
Trung Tien Phan ◽  
Trong Hanh Hoang ◽  
Van Tuan Mai ◽  
Xuan Chuong Tran
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infection ◽  
Resistant Bacteria ◽  
Central Hospital ◽  
International Consensus ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Results Of Treatment ◽  
Amoxicillin Clavulanic Acid ◽  
Relationship Of

Sepsis is a serious bacterial infection. The main treatment is using antibiotics. However, the rate of antibiotic resistance is very high and this resistance is related to the outcome of treatment. Objectives: To evaluate the situation of antibiotic resistance of some isolated bacteria in sepsis patients treated at Hue Central Hospital; to evaluate the relationship of antibiotic resistance to the treatment results in patients with sepsis. Subjects and methods: prospective study of 60 sepsis patients diagnosed according to the criteria of the 3rd International Consensus-Sepsis 3 and its susceptibility patterns from April 2017 to August 2018. Results and Conclusions: The current agents of sepsis are mainly S. suis, Burkhoderiae spp. and E. coli. E. coli is resistant to cephalosporins 3rd, 4th generation and quinolone group is over 75%; resistance to imipenem 11.1%; the ESBL rate is 60%. S. suis resistant to ampicilline 11.1%; no resistance has been recorded to ceftriaxone and vancomycine. Resistance of Burkholderiae spp. to cefepime and amoxicillin/clavulanic acid was 42.9% and 55.6%, resistant to imipenem and meropenem is 20%, resistance to ceftazidime was not recorded. The deaths were mostly dued to E. coli and K. pneumoniae. The mortality for patients infected with antibiotic-resistant bacteria are higher than for sensitive groups. Key words: Sepsis, bacterial infection, antibiotics

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