In Mycobacterium abscessus , the stringent factor Rel regulates metabolism, but is not the only (p)ppGpp synthase.

2021 ◽  
Author(s):  
Augusto César Hunt-Serracín ◽  
Misha I. Kazi ◽  
Joseph M. Boll ◽  
Cara C. Boutte
Keyword(s):  
Antibiotic Resistance ◽  
Stress Response ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Stringent Response ◽  
Mycobacterium Abscessus ◽  
Functional Roles ◽  
Metabolic Genes ◽  
Stress Response System

The stringent response is a broadly conserved stress response system that exhibits functional variability across bacterial clades. Here, we characterize the role of the stringent factor Rel in the non-tuberculous mycobacterial pathogen, Mycobacterium abscessus ( Mab ). We found that deletion of rel does not ablate (p)ppGpp synthesis, and that rel does not provide a survival advantage in several stress conditions, or in antibiotic treatment. Transcriptional data show that Rel Mab is involved in regulating expression of anabolism and growth genes in stationary phase. However, it does not activate transcription of stress response or antibiotic resistance genes, and actually represses transcription of many antibiotic resistance genes. This work shows that there is an unannotated (p)ppGpp synthetase in Mab . Importance In this study, we examined the functional roles of the stringent factor Rel in Mycobacterium abscessus (Mab) . In most species, stringent factors synthesize the alarmone (p)ppGpp, which globally alters transcription to promote growth arrest and survival under stress and in antibiotic treatment. Our work shows that in Mab, an emerging pathogen which is resistant to many antibiotics, the stringent factor Rel is not solely responsible for synthesizing (p)ppGpp. We find that Rel Mab downregulates many metabolic genes under stress, but does not upregulate stress response genes and does not promote antibiotic tolerance. This study implies that there is another critical but unannotated (p)ppGpp synthetase in Mab, and suggests that Rel Mab inhibitors are unlikely to sensitize Mab infections to antibiotic treatment.

scholarly journals The stringent factor Rel from Mycobacterium abscessus regulates metabolism, but does not promote survival in stress or antibiotics

2020 ◽  
Author(s):  
Augusto Cesar Hunt-Serracín ◽  
Joseph M. Boll ◽  
Cara C. Boutte
Keyword(s):  
Antibiotic Resistance ◽  
Stress Response ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Transcriptional Profiling ◽  
Antibiotic Resistance Genes ◽  
Stringent Response ◽  
Mycobacterium Abscessus ◽  
Stress Response System

AbstractThe stringent response is a broadly conserved stress response system that exhibits functional variability across bacterial clades. Here, we characterize the role of the stringent factor Rel in the non-tuberculous mycobacterial pathogen, Mycobacterium abscessus (Mab). We find that Rel in Mab is involved in restricting transcription of anabolism and growth genes in stress, as has been observed in many other species. However, the stringent response in Mab does not provide a survival advantage in several stress conditions or in antibiotic treatment. According to our transcriptional profiling, Rel in Mab does not activate transcription of stress response or antibiotic resistance genes. Instead, Rel actually represses transcription of many antibiotic resistance genes in stress. This study implies that combinatorial therapies with stringent factor inhibitors would not potentiate antibiotic treatment against Mab infections.

scholarly journals Antibiotic Resistance Genes in Lemur Gut and Soil Microbiota Along a Gradient of Anthropogenic Disturbance

2021 ◽  
Vol 9 ◽  
Author(s):  
Sally L. Bornbusch ◽  
Christine M. Drea
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Anthropogenic Disturbance ◽  
Antibiotic Resistance Genes ◽  
Single Species ◽  
The United States ◽  
Metagenomic Sequencing ◽  
Natural Habitats ◽  
Human Contact

The overuse of man-made antibiotics has facilitated the global propagation of antibiotic resistance genes in animals, across natural and anthropogenically disturbed environments. Although antibiotic treatment is the most well-studied route by which resistance genes can develop and spread within host-associated microbiota, resistomes also can be acquired or enriched via more indirect routes, such as via transmission between hosts or via contact with antibiotic-contaminated matter within the environment. Relatively little is known about the impacts of anthropogenic disturbance on reservoirs of resistance genes in wildlife and their environments. We therefore tested for (a) antibiotic resistance genes in primate hosts experiencing different severities and types of anthropogenic disturbance (i.e., non-wildlife animal presence, human presence, direct human contact, and antibiotic treatment), and (b) covariation between host-associated and environmental resistomes. We used shotgun metagenomic sequencing of ring-tailed lemur (Lemur catta) gut resistomes and associated soil resistomes sampled from up to 10 sites: seven in the wilderness of Madagascar and three in captivity in Madagascar or the United States. We found that, compared to wild lemurs, captive lemurs harbored greater abundances of resistance genes, but not necessarily more diverse resistomes. Abundances of resistance genes were positively correlated with our assessments of anthropogenic disturbance, a pattern that was robust across all ten lemur populations. The composition of lemur resistomes was site-specific and the types of resistance genes reflected antibiotic usage in the country of origin, such as vancomycin use in Madagascar. We found support for multiple routes of ARG enrichment (e.g., via human contact, antibiotic treatment, and environmental acquisition) that differed across lemur populations, but could result in similar degrees of enrichment. Soil resistomes varied across natural habitats in Madagascar and, at sites with greater anthropogenic disturbance, lemurs and soil resistomes covaried. As one of the broadest, single-species investigations of wildlife resistomes to date, we show that the transmission and enrichment of antibiotic resistance genes varies across environments, thereby adding to the mounting evidence that the resistance crisis extends outside of traditional clinical settings.

scholarly journals Extended antibiotic treatment in salmon farms select multiresistant gut bacteria with a high prevalence of antibiotic resistance genes

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0203641 ◽  
Author(s):  
Sebastián Higuera-Llantén ◽  
Felipe Vásquez-Ponce ◽  
Beatriz Barrientos-Espinoza ◽  
Fernando O. Mardones ◽  
Sergio H. Marshall ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Antibiotic Treatment ◽  
Resistance Genes ◽  
Antibiotic Resistance Genes ◽  
Gut Bacteria ◽  
High Prevalence

Quintuplex PCR to Detect Antibiotic Resistance Genes in Streptococcus pneumoniae

2016 ◽  
Vol 1 (2) ◽  
pp. 22 ◽  
Author(s):  
Navindra Kumari Palanisamy ◽  
Parasakthi Navaratnam ◽  
Shamala Devi Sekaran
Keyword(s):  
Antibiotic Resistance ◽  
Streptococcus Pneumoniae ◽  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Antibiotic Resistance Genes ◽  
Pcr Amplification ◽  
Penicillin Resistance ◽  
Penicillin Binding Proteins ◽  
Efflux Mechanism ◽  
Mic Value

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.

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