scholarly journals Control of Genome Stability by EndoMS/NucS-Mediated Non-Canonical Mismatch Repair

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1314
Author(s):  
Esmeralda Cebrián-Sastre ◽  
Isabel Martín-Blecua ◽  
Sonia Gullón ◽  
Jesús Blázquez ◽  
Alfredo Castañeda-García
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Mismatch Repair ◽  
Genome Stability ◽  
Recent Progress ◽  
Resistant Bacteria ◽  
Sliding Clamp ◽  
Mismatched Base Pair ◽  
Homeologous Recombination ◽  
New Strategies

The DNA repair endonuclease EndoMS/NucS is highly conserved in Archaea and Actinobacteria. This enzyme is able to recognize and cleave dsDNA carrying a mismatched base pair, and its activity is enhanced by the interaction with the sliding clamp of the replisome. Today, EndoMS/NucS has been established as the key protein of a non-canonical mismatch repair (MMR) pathway, acting specifically in the repair of transitions and being essential for maintaining genome stability. Despite having some particularities, such as its lower activity on transversions and the inability to correct indels, EndoMS/NucS meets the main hallmarks of a MMR. Its absence leads to a hypermutator phenotype, a transition-biased mutational spectrum and an increase in homeologous recombination. Interestingly, polymorphic EndoMS/NucS variants with a possible effect in mutation rate have been detected in clinical isolates of the relevant actinobacterial pathogen Mycobacterium tuberculosis. Considering that MMR defects are often associated with the emergence of resistant bacteria, the existence of EndoMS/NucS-defective mutators could have an important role in the acquisition of antibiotic resistance in M. tuberculosis. Therefore, a further understanding of the EndoMS/NucS-mediated non-canonical MMR pathway may reveal new strategies to predict and fight drug resistance. This review is focused on the recent progress in NucS, with special emphasis on its effect on genome stability and evolvability in Actinobacteria.

scholarly journals Two Lytic Bacteriophages That Depend on theEscherichia coliMulti-Drug Efflux GenetolCand Differentially Affect Bacterial Growth and Selection

2018 ◽  
Author(s):  
Alita R. Burmeister ◽  
Rose G. Bender ◽  
Abigail Fortier ◽  
Adam J. Lessing ◽  
Benjamin K. Chan ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Resistance Gene ◽  
Bacterial Growth ◽  
Bacterial Pathogens ◽  
Antibiotic Resistance Gene ◽  
Resistant Bacteria ◽  
Drug Efflux ◽  
Drug Resistant ◽  
Resistant Mutants

AbstractBacterial pathogens are increasingly evolving drug resistance under natural selection from antibiotics in medicine, agriculture, and nature. Meanwhile, bacteria ubiquitously encounter bacteriophages and can rapidly evolve phage resistance. However, the role of phages in interacting with drug-resistant and drug-sensitive bacteria remains unclear. To gain insight into such relationships, we screened for and characterized phages that rely on the multi-drug efflux pump genetolC. First, we screened a collection of 33 environmental and commercialEscherichia coliphages for their ability to infect cells that lackedtolC. Our screen revealed two phages that had reduced efficiency of plating (EOP) on thetolCknockout compared to wild type. We further characterized these phages with bacterial growth curves, transmission electron microscopy, and analysis of phage-resistant mutants. Phage U136B is a curly-tailed virus in familySiphoviridaewith no ability to infect atolCknockout, suggesting TolC is the U136B receptor. Phage 132 is a contractile-tailed virus in familyMyoviridaewith reduced EOP on cells lackingompFand its positive regulatorstolCandompR. U136B and 132 differentially effect bacterial growth and lysis, and U136B-resistant mutants contain mutations of thetolCgene. Together, these results show that thetolCgene involved in drug resistance can modify bacteria-phage interactions in multiple ways, altering bacterial lysis and selection. These new phages offer utility for studying evolution, tradeoffs, and infection mechanisms.ImportanceBacteria face strong selection by antibiotics in medicine and agriculture, resulting in increasing levels of drug resistance among bacterial pathogens. Slowing this process will require an understanding of the environmental contexts in which drug resistance evolutionarily increases or decreases. In this study, we investigate two newly-isolated bacteriophages that rely on a bacterial antibiotic resistance gene. These bacteriophages vary in their interactions with drug-resistant bacteria, with one of the phages selecting for phage-resistant mutants that have mutations in the antibiotic resistance gene. Further study of these new phages will be useful to understanding evolutionary tradeoffs and how phages might be applied in natural settings to reverse the problem of drug resistance.

scholarly journals Review on Multiple Facets of Drug Resistance: A Rising Challenge in the 21st Century

2021 ◽  
Vol 11 (4) ◽  
pp. 197-214
Author(s):  
Mousumi Saha ◽  
Agniswar Sarkar
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Bacterial Infections ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Relevant Information ◽  
High Rate ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Potential Threat

With the advancements of science, antibiotics have emerged as an amazing gift to the human and animal healthcare sectors for the treatment of bacterial infections and other diseases. However, the evolution of new bacterial strains, along with excessive use and reckless consumption of antibiotics have led to the unfolding of antibiotic resistances to an excessive level. Multidrug resistance is a potential threat worldwide, and is escalating at an extremely high rate. Information related to drug resistance, and its regulation and control are still very little. To interpret the onset of antibiotic resistances, investigation on molecular analysis of resistance genes, their distribution and mechanisms are urgently required. Fine-tuned research and resistance profile regarding ESKAPE pathogen is also necessary along with other multidrug resistant bacteria. In the present scenario, the interaction of bacterial infections with SARS-CoV-2 is also crucial. Tracking and in-silico analysis of various resistance mechanisms or gene/s are crucial for overcoming the problem, and thus, the maintenance of relevant databases and wise use of antibiotics should be promoted. Creating awareness of this critical situation among individuals at every level is important to strengthen the fight against this fast-growing calamity. The review aimed to provide detailed information on antibiotic resistance, its regulatory molecular mechanisms responsible for the resistance, and other relevant information. In this article, we tried to focus on the correlation between antimicrobial resistance and the COVID-19 pandemic. This study will help in developing new interventions, potential approaches, and strategies to handle the complexity of antibiotic resistance and prevent the incidences of life-threatening infections.

scholarly journals Drug resistance and plasmid profile of bacterial isolates from automated teller machine keypads in Benin city

2019 ◽  
Vol 54 (3) ◽  
pp. 231-240
Author(s):  
FI Akinnibosun ◽  
JA Adetitun
Keyword(s):  
Escherichia Coli ◽  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Micrococcus Luteus ◽  
Plasmid Profile ◽  
Resistant Bacteria ◽  
Bacterial Isolates ◽  
Benin City ◽  
Automated Teller Machine ◽  
Mar Index

The purpose of this study was to investigate the drug resistance and plasmid profile of bacterial isolates from automated teller machine (ATM) keypads in Benin City, Nigeria. Samples were collected from the keypads of ATMs situated in banking premises and open access areas using stratified random sampling method at 5 different locations. Isolated bacteria were characterized by extensive phenotypic and biochemical identification procedures. Antibiotic susceptibility pattern and plasmid profile of the isolates were carried out using standard methods. The bacteria isolated were: Klebsiella sp., Pseudomonas aeruginosa, Proteus vulgaris, Escherichia coli, Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus, Corynebacteria sp., Staphylococcus epidermidis and Streptococcus pyogenes. Each isolate exhibited marked resistance to the antibiotics, with multiple antibiotic resistance (MAR) index > 0.2. Escherichia coli showed the highest resistance (MAR index, 1) while Micrococcus luteus exhibited the least resistance (MAR index, 0.5) to the antibiotics used. Plasmid profile of the isolates revealed the presence of plasmids in the isolates, with a reduction in antibiotic resistance after plasmid curing in some isolates. This indicated plasmid-mediated resistance among majority of the isolates. From the results obtained, it is pertinent therefore, to adopt proper measures aimed at preventing outbreak of diseases associated with these multi-drug resistant bacteria isolated from ATM keypads. Bangladesh J. Sci. Ind. Res.54(3), 231-240, 2019

scholarly journals Anti-plasmid activity of Chlorpromazine in types of antibiotics resistant pathogenic bacteria

2021 ◽  
Vol 26 (4) ◽  
Author(s):  
Alaa Qasim ◽  
Muhsin Ayoub Essa
Keyword(s):  
Antibiotic Resistance ◽  
Pathogenic Bacteria ◽  
Diffusion Method ◽  
Resistance Pattern ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Bacterial Strains ◽  
Before And After ◽  
Bacteria Resistance ◽  
New Strategies

This study was performed to evaluate the ability of chlorpromazine compound to cure the plasmids and remove the antibiotic resistance character of multidrug resistance Gram-negative pathogenic bacteria. The curing experiment was done by incubating bacterial strains in nutrient broth with sub MIC concentration of chlorpromazine, and the disc diffusion method was used before and after curing to evaluate antibiotic resistance pattern of bacteria. Synergetic test of chlorpromazine with antibiotics that the studied bacteria showed resistance toward also done. The results showed the ability of chlorpromazine to remove the plasmids from four bacterial genera out of five genera, where the most plasmid removal cases was with E.cloacae, P.aeruginosa, and P.merabilis, and the loss of antibiotics resistance was observed in the same bacterial genera, but P.merabilis showed the most antibiotics resistance losing by three antibiotics out of nine antibiotics that the bacteria were resistant to them before curing. As for the synergistic effect, the compound showed a synergism with only two antibiotic and with the three aforementioned bacterial genera. From results of this study we concluded the possibility of removing bacteria resistance to antibiotics by eliminating plasmids through using chlorpromazine, and the possibility of using this compound in synergism with antibiotics, this will open the way to find new strategies  to treat many diseases caused by resistant bacteria.

The gut microbiota resistome provides development of drug resistance in causative agents of human infectious diseases

2017 ◽  
pp. 20-32 ◽  
Author(s):  
Е.Н. Ильина ◽  
Е.И. Олехнович ◽  
А.В. Павленко
Keyword(s):  
Drug Resistance ◽  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Integrated Approach ◽  
Modern Medicine ◽  
Pathogenic Microorganisms ◽  
Human Pathogens ◽  
Potential Source ◽  
Causative Agents ◽  
Bacterial Genes

С течением времени подходы к изучению резистентности к антибиотикам трансформировались от сосредоточения на выделенных в виде чистой культуры патогенных микроорганизмах к исследованию резистентности на уровне микробных сообществ, составляющих биотопы человека и окружающей среды. По мере того, как продвигается изучение устойчивости к антибиотикам, возникает необходимость использования комплексного подхода для улучшения информирования мирового сообщества о наблюдаемых тенденциях в этой области. Все более очевидным становится то, что, хотя не все гены резистентности могут географически и филогенетически распространяться, угроза, которую они представляют, действительно серьезная и требует комплексных междисциплинарных исследований. В настоящее время резистентность к антибиотикам среди патогенов человека стала основной угрозой в современной медицине, и существует значительный интерес к определению ниши, в которых бактерии могут получить гены антибиотикорезистентности, и механизмов их передачи. В данном обзоре мы рассматриваем проблемы, возникшие на фоне широкого использования человечеством антибактериальных препаратов, в свете формирования микрофлорой кишечника резервуара генов резистентности. Over the time, studies of antibiotic resistance have transformed from focusing on pathogenic microorganisms isolated as a pure culture to analysis of resistance at the level of microbial communities that constitute human and environmental biotopes. Advancing studies of antibiotic resistance require an integrated approach to enhance availability of information about observed tendencies in this field to the global community. It becomes increasingly obvious that, even though not all resistance genes can geographically and phylogenetically spread, the threat they pose is indeed serious and requires complex interdisciplinary research. Currently, the antibiotic resistance of human pathogens has become a challenge to modern medicine, which is now focusing on determining a potential source for bacterial genes of drug resistance and mechanisms for the gene transmission. In this review, we discussed problems generated by the widespread use of antibacterial drugs in the light of forming a reservoir of resistance genes by gut microflora.

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 Recent Progress in Characterizing Long Noncoding RNAs in Cancer Drug Resistance

2019 ◽  
Vol 10 (26) ◽  
pp. 6693-6702 ◽  
Author(s):  
Wenyuan Zhao ◽  
Bin Shan ◽  
Dan He ◽  
Yuanda Cheng ◽  
Bin Li ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Recent Progress ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cancer Drug ◽  
Cancer Drug Resistance

scholarly journals Assessing the Molecular Targets and Mode of Action of Furanone C-30 on Pseudomonas aeruginosa Quorum Sensing

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1620
Author(s):  
Victor Markus ◽  
Karina Golberg ◽  
Kerem Teralı ◽  
Nazmi Ozer ◽  
Esti Kramarsky-Winter ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Quorum Sensing ◽  
Conformational Changes ◽  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Molecular Targets ◽  
Resistant Bacteria ◽  
Public Healthcare ◽  
C 30

Quorum sensing (QS), a sophisticated system of bacterial communication that depends on population density, is employed by many pathogenic bacteria to regulate virulence. In view of the current reality of antibiotic resistance, it is expected that interfering with QS can address bacterial pathogenicity without stimulating the incidence of resistance. Thus, harnessing QS inhibitors has been considered a promising approach to overriding bacterial infections and combating antibiotic resistance that has become a major threat to public healthcare around the globe. Pseudomonas aeruginosa is one of the most frequent multidrug-resistant bacteria that utilize QS to control virulence. Many natural compounds, including furanones, have demonstrated strong inhibitory effects on several pathogens via blocking or attenuating QS. While the natural furanones show no activity against P. aeruginosa, furanone C-30, a brominated derivative of natural furanone compounds, has been reported to be a potent inhibitor of the QS system of the notorious opportunistic pathogen. In the present study, we assess the molecular targets and mode of action of furanone C-30 on P. aeruginosa QS system. Our results suggest that furanone C-30 binds to LasR at the ligand-binding site but fails to establish interactions with the residues crucial for the protein’s productive conformational changes and folding, thus rendering the protein dysfunctional. We also show that furanone C-30 inhibits RhlR, independent of LasR, suggesting a complex mechanism for the agent beyond what is known to date.

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