scholarly journals Salicylate increases fitness cost associated with MarA-mediated antibiotic resistance

2018 ◽  
Author(s):  
T. Wang ◽  
C. Kunze ◽  
M. J. Dunlop
Keyword(s):  
Antibiotic Resistance ◽  
Wide Spectrum ◽  
Environmental Chemicals ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Important Regulator ◽  
Quantitative Understanding ◽  
Resistant Strains ◽  
The Cost

AbstractAntibiotic resistance is generally associated with a fitness deficit resulting from the burden of producing and maintaining resistance machinery. This additional cost suggests that resistant bacteria will be outcompeted by susceptible bacteria in conditions without antibiotics. However, in practice this process is slow due in part to regulation that minimizes expression of these genes in the absence of antibiotics. This suggests that if it were possible to turn on their expression, the cost would increase, thereby accelerating removal of resistant strains. Experimental and theoretical studies have shown that environmental chemicals can change the fitness cost associated with resistance and therefore have a significant impact on population dynamics. MarA (multiple antibiotic resistance activator) is a clinically important regulator in Escherichia coli which activates downstream genes to increase resistance against multiple classes of antibiotics. Salicylate is an inducer of MarA which can be found in the environment and de-represses marA’s expression. In this study, we sought to unravel the interplay between salicylate and the fitness cost of MarA-mediated antibiotic resistance. Using salicylate as a natural inducer of MarA, we found that a wide spectrum of concentrations can increase burden in resistant strains compared to susceptible strains. Induction resulted in rapid exclusion of resistant bacteria from mixed populations of antibiotic resistant and susceptible cells. A mathematical model captures the process and predicts its effect in various environmental conditions. Our work provides a quantitative understanding of salicylate exposure on the fitness of different MarA variants, and suggests that salicylate can lead to selection against MarA-mediated resistant strains. More generally, our findings show that natural inducers may serve to bias population membership and could impact antibiotic resistance and other important phenotypes.

scholarly journals Thinking Outside the Bug: Molecular Targets and Strategies to Overcome Antibiotic Resistance

2019 ◽  
Vol 20 (6) ◽  
pp. 1255 ◽  
Author(s):  
Ana Monserrat-Martinez ◽  
Yann Gambin ◽  
Emma Sierecki
Keyword(s):  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Rational Design ◽  
Disease Onset ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
New Antibiotics ◽  
Resistant Strains ◽  
Vancomycin Resistant ◽  
Antibiotic Discovery

Since their discovery in the early 20th century, antibiotics have been used as the primary weapon against bacterial infections. Due to their prophylactic effect, they are also used as part of the cocktail of drugs given to treat complex diseases such as cancer or during surgery, in order to prevent infection. This has resulted in a decrease of mortality from infectious diseases and an increase in life expectancy in the last 100 years. However, as a consequence of administering antibiotics broadly to the population and sometimes misusing them, antibiotic-resistant bacteria have appeared. The emergence of resistant strains is a global health threat to humanity. Highly-resistant bacteria like Staphylococcus aureus (methicillin-resistant) or Enterococcus faecium (vancomycin-resistant) have led to complications in intensive care units, increasing medical costs and putting patient lives at risk. The appearance of these resistant strains together with the difficulty in finding new antimicrobials has alarmed the scientific community. Most of the strategies currently employed to develop new antibiotics point towards novel approaches for drug design based on prodrugs or rational design of new molecules. However, targeting crucial bacterial processes by these means will keep creating evolutionary pressure towards drug resistance. In this review, we discuss antibiotic resistance and new options for antibiotic discovery, focusing in particular on new alternatives aiming to disarm the bacteria or empower the host to avoid disease onset.

scholarly journals Antibiotic Resistance of Gram-Negative Bacteria from Wild Captured Loggerhead Sea Turtles

Antibiotics ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 162 ◽  
Author(s):  
Monica Francesca Blasi ◽  
Luciana Migliore ◽  
Daniela Mattei ◽  
Alice Rotini ◽  
Maria Cristina Thaller ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Sea Turtles ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Marine Animals ◽  
Loggerhead Sea Turtles ◽  
Antibiotic Resistant ◽  
Gram Negative ◽  
Marine Habitats ◽  
Resistant Strains

Sea turtles have been proposed as health indicators of marine habitats and carriers of antibiotic-resistant bacterial strains, for their longevity and migratory lifestyle. Up to now, a few studies evaluated the antibacterial resistant flora of Mediterranean loggerhead sea turtles (Caretta caretta) and most of them were carried out on stranded or recovered animals. In this study, the isolation and the antibiotic resistance profile of 90 Gram negative bacteria from cloacal swabs of 33 Mediterranean wild captured loggerhead sea turtles are described. Among sea turtles found in their foraging sites, 23 were in good health and 10 needed recovery for different health problems (hereafter named weak). Isolated cloacal bacteria belonged mainly to Enterobacteriaceae (59%), Shewanellaceae (31%) and Vibrionaceae families (5%). Although slight differences in the bacterial composition, healthy and weak sea turtles shared antibiotic-resistant strains. In total, 74 strains were endowed with one or multi resistance (up to five different drugs) phenotypes, mainly towards ampicillin (~70%) or sulfamethoxazole/trimethoprim (more than 30%). Hence, our results confirmed the presence of antibiotic-resistant strains also in healthy marine animals and the role of the loggerhead sea turtles in spreading antibiotic-resistant bacteria.

scholarly journals Persistence of Transferable Extended-Spectrum-β-Lactamase Resistance in the Absence of Antibiotic Pressure

2012 ◽  
Vol 56 (9) ◽  
pp. 4703-4706 ◽  
Author(s):  
Jennifer L. Cottell ◽  
Mark A. Webber ◽  
Laura J. V. Piddock
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Fitness Cost ◽  
Resistant Bacteria ◽  
Bacterial Host ◽  
Antibiotic Resistant ◽  
M 14 ◽  
Host Strains

ABSTRACTThe treatment of infections caused by antibiotic-resistant bacteria is one of the great challenges faced by clinicians in the 21st century. Antibiotic resistance genes are often transferred between bacteria by mobile genetic vectors called plasmids. It is commonly believed that removal of antibiotic pressure will reduce the numbers of antibiotic-resistant bacteria due to the perception that carriage of resistance imposes a fitness cost on the bacterium. This study investigated the ability of the plasmid pCT, a globally distributed plasmid that carries an extended-spectrum-β-lactamase (ESBL) resistance gene (blaCTX-M-14), to persist and disseminate in the absence of antibiotic pressure. We investigated key attributes in plasmid success, including conjugation frequencies, bacterial-host growth rates, ability to cause infection, and impact on the fitness of host strains. We also determined the contribution of theblaCTX-M-14gene itself to the biology of the plasmid and host bacterium. Carriage of pCT was found to impose no detectable fitness cost on various bacterial hosts. An absence of antibiotic pressure and inactivation of the antibiotic resistance gene also had no effect on plasmid persistence, conjugation frequency, or bacterial-host biology. In conclusion, plasmids such as pCT have evolved to impose little impact on host strains. Therefore, the persistence of antibiotic resistance genes and their vectors is to be expected in the absence of antibiotic selective pressure regardless of antibiotic stewardship. Other means to reduce plasmid stability are needed to prevent the persistence of these vectors and the antibiotic resistance genes they carry.

scholarly journals Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Susanne Schjørring ◽  
Karen A. Krogfelt
Keyword(s):  
Antibiotic Resistance ◽  
Gene Transfer ◽  
Resistance Genes ◽  
Bacterial Flora ◽  
Antibiotic Resistance Genes ◽  
Resistant Bacteria ◽  
Gi Tract ◽  
Antibiotic Resistant ◽  
Multiresistant Bacteria ◽  
Resistant Strains

We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut.

scholarly journals Antibiotic-resistant microbiota of water and soil ecosystems as risk factors for human health

2021 ◽  
Vol 32 (1) ◽  
pp. 67-70
Author(s):  
T. Yu. Matylonok ◽  
O. Ye. Pakhomov ◽  
N. M. Polishchuck
Keyword(s):  
Antibiotic Resistance ◽  
Human Health ◽  
Resistance Genes ◽  
Large Scale ◽  
Resistant Bacteria ◽  
Antibacterial Drugs ◽  
Antibiotic Resistant ◽  
Soil Ecosystems ◽  
The World ◽  
Resistant Strains

Bacterial resistance to antibiotics is one of the three major health challenges of the 21st century. One of the most important reasons for the acquisition and spread of antibiotic resistance in the environment is the irrational and uncontrolled use of antibacterial drugs, not only for medical but also other purposes, and their improper disposal. The microbiome of aquatic and soil ecosystems is characterized by the acquisition of antibiotic resistance through mobile genetic elements, contact with antibacterial drugs and their residues, the action of heavy metals and environmental stress. Also, according to the literature, it is noted that the resistance of microorganisms to antibacterial drugs in the environment existed much earlier than in clinical strains. These facts can not help but worry, because antibiotic-resistant strains of the environment have an extremely negative impact on human health. Once in the human body with water and food, they significantly complicate and / or make it impossible to further treat life-threatening diseases. Also, antibacterial residues circulating in aquatic and soil ecosystems, entering the human body can cause cancer, allergic reactions or disruption of the natural intestinal microflora. These ecosystems are characterized by large-scale spread of antibiotic-resistant microorganisms, antibacterial drugs and their residues. The aim of our work was to analyze with the help of theoretical methods of scientific research the reasons for the acquisition and spread of antibiotic resistance among environmental microbiota, namely in aquatic and soil ecosystems. To determine the impact of antibiotic-resistant bacteria of these ecosystems on human health. We have found that antibacterial drugs, antibiotic-resistant strains and resistance genes are a particular problem for wastewater treatment. Antibiotics can provide a selective load, as the mechanisms that break them down can promote resilience and selectively enrich. Wastewater treatment plants can be a favorable factor for the horizontal transfer of genes and the development of bacterial polyresistance, and high-resistance genes can be preserved even after disinfection. Soil is also an important reservoir for antibiotic-resistant bacteria and resistance genes. Microorganisms are in a constant struggle for existence in this ecosystem and try to colonize the micro-scale with the most favorable for their ecotype habitat. Antibiotic-resistant soil bacteria are in close contact with other members of the microbiota, which in turn promotes the horizontal transfer of resistance genes, even between cells of different species or genera through genetic determinants. Conclusion: ecosystems are characterized by large-scale spread of antibiotic-resistant microorganisms, antibacterial drugs and their residues. Therefore, this problem should be properly addressed, as the presence of antibiotic-resistant microorganisms, antibacterial drugs and their residues in the environment can cause unpredictable environmental consequences and adversely affect human health with more severe incurable infectious diseases. Monitoring programs for antibiotic-resistant microorganisms and resistance genes in soil and aquatic ecosystems are necessary and very relevant today. After all, this microbiota poses a serious threat to both the environment and human health and can easily spread from one part of the world around the world.

scholarly journals Antibiotic Resistance Increases Evolvability and Maximizes Opportunities Across Fitness Landscapes

2019 ◽  
Author(s):  
Fabrizio Spagnolo ◽  
Daniel E. Dykhuizen
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Public Health Problem ◽  
Fitness Landscapes ◽  
Resistant Bacteria ◽  
Major Question ◽  
Antibiotic Resistant ◽  
Resistant Strains ◽  
Compensatory Mutations ◽  
Selection For

AbstractAntibiotic resistance continues to grow as a public health problem. One of the reasons for this continued growth is that resistance to antibiotics is strongly selected for in the presence of antibiotics and weakly selected against after their removal. This is frequently thought to be due to the effects of compensatory mutations. However, compensatory mutations are often not found in clinically relevant strains of antibiotic resistant pathogens. Here, we conduct experiments in vitro that highlight the role that fine scale differences in environment play in the maintenance of populations after selection for resistance. We show that differences in the mode of growth, dictated by environmental factors, are capable of reliably changing the force and direction of selection. Our results show that antibiotic resistance can increase evolvability in environments if conditions for selection exist, selecting differentially for newly arising variation and moving populations to previously unavailable adaptive peaks.SignificanceAntibiotic resistant bacteria are a large and growing problem for public health. A major question has been why antibiotic resistant strains do not disappear when they must compete with higher fitness drug sensitive strains. Here we show that selection for antibiotic resistant strains is particularly sensitive to differences in environmental conditions and that these differences help to define the fitness landscapes upon which these populations adapt. The result is an increase in evolvability, with many adaptive peaks that drug resistant populations can explore through natural selection, making predictions of evolution difficult and selection against resistant strains improbable.

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

scholarly journals Testudines as Sentinels for Monitoring the Dissemination of Antibiotic Resistance in Marine Environments: An Integrative Review

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 775
Author(s):  
Kezia Drane ◽  
Roger Huerlimann ◽  
Michelle Power ◽  
Anna Whelan ◽  
Ellen Ariel ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Anthropogenic Activities ◽  
Sea Turtles ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Marine Environments ◽  
Beta Lactam ◽  
Antibiotic Resistant ◽  
Sensitivity Tests ◽  
Standard Culture

Dissemination of antibiotic resistance (AR) in marine environments is a global concern with a propensity to affect public health and many ecosystems worldwide. We evaluated the use of sea turtles as sentinel species for monitoring AR in marine environments. In this field, antibiotic-resistant bacteria have been commonly identified by using standard culture and sensitivity tests, leading to an overrepresentation of specific, culturable bacterial classes in the available literature. AR was detected against all major antibiotic classes, but the highest cumulative global frequency of resistance in all represented geographical sites was against the beta-lactam class by a two-fold difference compared to all other antibiotics. Wastewater facilities and turtle rehabilitation centres were associated with higher incidences of multidrug-resistant bacteria (MDRB) accounting for an average of 58% and 49% of resistant isolates, respectively. Furthermore, a relatively similar prevalence of MDRB was seen in all studied locations. These data suggest that anthropogenically driven selection pressures for the development of AR in sea turtles and marine environments are relatively similar worldwide. There is a need, however, to establish direct demonstrable associations between AR in sea turtles in their respective marine environments with wastewater facilities and other anthropogenic activities worldwide.

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