Inside environmental Clostridium perfringens genomes: antibiotic resistance genes, virulence factors and genomic features

Abstract Until recently, research has focused on Clostridium perfringens in clinical settings without considering environmental isolates. In this study, environmental genomes were used to investigate possible antibiotic resistance and the presence of virulence traits in C. perfringens strains from raw surface water. In silico assembly of three C. perfringens strains, DNA generated almost complete genomes setting their length ranging from 3.4 to 3.6 Mbp with GC content of 28.18%. An average of 3,175 open reading frames was identified, with the majority associated with carbohydrate and protein metabolisms. The genomes harboured several antibiotic resistance genes for glycopeptides, macrolide–lincosamide–streptogramin B, β-lactam, trimethoprim, tetracycline and aminoglycosides and also the presence of several genes encoding for polypeptides and multidrug resistance efflux pumps and 35 virulence genes. Some of these encode for haemolysins, sialidase, hyaluronidase, collagenase, perfringolysin O and phospholipase C. All three genomes contained sequences indicating phage, antibiotic resistance and pathogenic islands integration sites. A genomic comparison of these three strains confirmed high similarity and shared core genes with clinical C. perfringens strains, highlighting their health security risks. This study provides a genomic insight into the potential pathogenicity of C. perfringens present in the environment and emphasises the importance of monitoring this niche in the future.

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Characterization of a Multiresistant Mosaic Plasmid from a Fish Farm Sediment Exiguobacterium sp. Isolate Reveals Aggregation of Functional Clinic-Associated Antibiotic Resistance Genes

Applied and Environmental Microbiology ◽

10.1128/aem.03257-13 ◽

2013 ◽

Vol 80 (4) ◽

pp. 1482-1488 ◽

Cited By ~ 9

Author(s):

Jing Yang ◽

Chao Wang ◽

Jinyu Wu ◽

Li Liu ◽

Gang Zhang ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Mobile Elements ◽

Fish Farms ◽

Significant Similarity ◽

Content Type ◽

Genes Encoding ◽

The Mean

ABSTRACTThe genusExiguobacteriumcan adapt readily to, and survive in, diverse environments. Our study demonstrated thatExiguobacteriumsp. strain S3-2, isolated from marine sediment, is resistant to five antibiotics. The plasmid pMC1 in this strain carries seven putative resistance genes. We functionally characterized these resistance genes inEscherichia coli, and genes encoding dihydrofolate reductase and macrolide phosphotransferase were considered novel resistance genes based on their low similarities to known resistance genes. The plasmid G+C content distribution was highly heterogeneous. Only the G+C content of one block, which shared significant similarity with a plasmid fromExiguobacterium arabatum, fit well with the mean G+C content of the host. The remainder of the plasmid was composed of mobile elements with a markedly lower G+C ratio than the host. Interestingly, five mobile elements located on pMC1 showed significant similarities to sequences found in pathogens. Our data provided an example of the link between resistance genes in strains from the environment and the clinic and revealed the aggregation of antibiotic resistance genes in bacteria isolated from fish farms.

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Mapping the regions carrying the three contiguous antibiotic resistance genes aadE, sat4, and aphA-3 in the genomes of staphylococci.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.5.1024 ◽

1997 ◽

Vol 41 (5) ◽

pp. 1024-1032 ◽

Cited By ~ 27

Author(s):

A Derbise ◽

S Aubert ◽

N El Solh

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Unknown Function ◽

Antibiotic Resistance Genes ◽

Open Reading Frames ◽

Restriction Fragments ◽

Internal Part ◽

Reading Frames ◽

Related Element

Tn5405 (12 kb) is a staphylococcal composite transposon delimited by two inverted copies of IS1182, one of which contains IS1181. The internal part of this transposon carries three antibiotic resistance genes, aphA-3, aadE, and sat4, and three open reading frames (ORFs), orfx, orfy, and orfz, of unknown function. The dispersion of Tn5405 and the genes and ORFs included in this transposon were investigated in 50 epidemiologically unrelated staphylococci carrying aphA-3. Twenty-three maps, distinguishable by the presence or absence of the investigated genes or ORFs and/or by the sizes of the restriction fragments carrying them, were identified. Four isolates carried Tn5405, and 15 other isolates contained a Tn5405-related element. IS1182 was not detected in the aphA-3 regions mapped in 31 isolates which carried the following combinations: orfx, orfy, aadE, sat4, and aphA-3 +/- orfz; orfy, aadE, sat4, and aphA-3 +/- orfz; and aadE, sat4, aphA-3, and orfz. In all isolates, the genes and ORFs investigated were in relative positions similar to those in Tn5405. Thus, the internal part of Tn5405 appeared to be partially conserved with the maintenance, in all of the isolates, of at least the three antibiotic resistance genes.

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Chloramphenicol Resistance in Clostridium difficile Is Encoded on Tn4453 Transposons That Are Closely Related to Tn4451 from Clostridium perfringens

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1563 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1563-1567 ◽

Cited By ~ 38

Author(s):

Dena Lyras ◽

Christine Storie ◽

Andrea S. Huggins ◽

Paul K. Crellin ◽

Trudi L. Bannam ◽

...

Keyword(s):

Antibiotic Resistance ◽

Clostridium Difficile ◽

Transposable Elements ◽

Clostridium Perfringens ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Nucleotide Sequencing ◽

Chloramphenicol Resistance ◽

Circular Form ◽

And Function

ABSTRACT The chloramphenicol resistance gene catD fromClostridium difficile was shown to be encoded on the transposons Tn4453a and Tn4453b, which were structurally and functionally related to Tn4451 fromClostridium perfringens. Tn4453a and Tn4453b excised precisely from recombinant plasmids, generating a circular form, as is the case for Tn4451. Evidence that this process is mediated by Tn4453-encodedtnpX genes was obtained from experiments which showed that in trans these genes complemented a Tn4451tnpXΔ1 mutation for excision. Nucleotide sequencing showed that the joint of the circular form generated by the excision of Tn4453a and Tn4453b was similar to that from Tn4451. These results suggest that the Tn4453-encoded TnpX proteins bind to similar DNA target sequences and function in a manner comparable to that of TnpX from Tn4451. Furthermore, it has been shown that Tn4453a and Tn4453b can be transferred to suitable recipient cells by RP4 and therefore are mobilizable transposons. It is concluded that, like Tn4451, they must encode a functional tnpZ gene and a targetoriT or RSA site. The finding that related transposable elements are present in C. difficile andC. perfringens has implications for the evolution and dissemination of antibiotic resistance genes and the mobile elements on which they are found within the clostridia.

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Characterization of antibiotic resistance genes in the species of the rumen microbiota

Nature Communications ◽

10.1038/s41467-019-13118-0 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Yasmin Neves Vieira Sabino ◽

Mateus Ferreira Santana ◽

Linda Boniface Oyama ◽

Fernanda Godoy Santos ◽

Ana Júlia Silva Moreira ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Animal Health ◽

Antibiotic Resistance Genes ◽

Tetracycline Resistance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Ruminal Bacteria ◽

Genes Encoding

AbstractInfections caused by multidrug resistant bacteria represent a therapeutic challenge both in clinical settings and in livestock production, but the prevalence of antibiotic resistance genes among the species of bacteria that colonize the gastrointestinal tract of ruminants is not well characterized. Here, we investigate the resistome of 435 ruminal microbial genomes in silico and confirm representative phenotypes in vitro. We find a high abundance of genes encoding tetracycline resistance and evidence that the tet(W) gene is under positive selective pressure. Our findings reveal that tet(W) is located in a novel integrative and conjugative element in several ruminal bacterial genomes. Analyses of rumen microbial metatranscriptomes confirm the expression of the most abundant antibiotic resistance genes. Our data provide insight into antibiotic resistange gene profiles of the main species of ruminal bacteria and reveal the potential role of mobile genetic elements in shaping the resistome of the rumen microbiome, with implications for human and animal health.

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Draft Genome Sequence of Corynebacterium aurimucosum UMB7769, Isolated from the Female Urinary Tract

Microbiology Resource Announcements ◽

10.1128/mra.00391-20 ◽

2020 ◽

Vol 9 (22) ◽

Author(s):

Samantha Eskandar ◽

Taylor Miller-Ensminger ◽

Adelina Voukadinova ◽

Alan J. Wolfe ◽

Catherine Putonti

Keyword(s):

Antibiotic Resistance ◽

Urinary Tract ◽

Genome Sequence ◽

Resistance Genes ◽

Draft Genome ◽

Gc Content ◽

Antibiotic Resistance Genes ◽

Draft Genome Sequence ◽

Content Type ◽

Female Urinary Tract

ABSTRACT Here, we present the draft genome sequence of Corynebacterium aurimucosum UMB7769, isolated from the female urinary tract. The size of the genome is 2,731,818 bp, assembled in 50 contigs, with an observed GC content of 60.9% and an N50 score of 129,518 bp. Annotation revealed 31 antibiotic resistance genes.

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Structural analysis of avibactam-mediated activation of the bla and mec divergons in methicillin-resistant Staphylococcus aureus

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.013029 ◽

2020 ◽

Vol 295 (32) ◽

pp. 10870-10884 ◽

Cited By ~ 2

Author(s):

J. Andrew N. Alexander ◽

Mariia Radaeva ◽

Dustin T. King ◽

Henry F. Chambers ◽

Artem Cherkasov ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Antibiotic Resistance ◽

Resistance Genes ◽

Physiological Role ◽

Antibiotic Resistance Genes ◽

Binding Pocket ◽

Methicillin Resistant ◽

Mortality And Morbidity ◽

Expression Of Genes ◽

Genes Encoding

Methicillin-resistant Staphylococcus aureus (MRSA) infections cause significant mortality and morbidity globally. MRSA resistance to β-lactam antibiotics is mediated by two divergons that control levels of a β-lactamase, PC1, and a penicillin-binding protein poorly acylated by β-lactam antibiotics, PBP2a. Expression of genes encoding these proteins is controlled by two integral membrane proteins, BlaR1 and MecR1, which both have an extracellular β-lactam–binding sensor domain. Here, we solved the X-ray crystallographic structures of the BlaR1 and MecR1 sensor domains in complex with avibactam, a diazabicyclooctane β-lactamase inhibitor at 1.6–2.0 Å resolution. Additionally, we show that S. aureus SF8300, a clinically relevant strain from the USA300 clone of MRSA, responds to avibactam by up-regulating the expression of the blaZ and pbp2a antibiotic-resistance genes, encoding PC1 and PBP2a, respectively. The BlaR1–avibactam structure of the carbamoyl-enzyme intermediate revealed that avibactam is bound to the active-site serine in two orientations ∼180° to each other. Although a physiological role of the observed alternative pose remains to be validated, our structural results hint at the presence of a secondary sulfate-binding pocket that could be exploited in the design of future inhibitors of BlaR1/MecR1 sensor domains or the structurally similar class D β-lactamases. The MecR1–avibactam structure adopted a singular avibactam orientation similar to one of the two states observed in the BlaR1–avibactam structure. Given avibactam up-regulates expression of blaZ and pbp2a antibiotic resistance genes, we suggest further consideration and research is needed to explore what effects administering β-lactam–avibactam combinations have on treating MRSA infections.

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Case report: Detection of aadB and tet (39) on the plasmid of Acinetobacter baumannii TN81 in Vietnam through next-generation sequencing and bioinformatics analysis

Tạp chí Y học Dự phòng ◽

10.51403/0868-2836/2021/336 ◽

2021 ◽

Vol 31 (4) ◽

pp. 51-60

Author(s):

Vu Nhi Ha ◽

Kieu Chi Thanh ◽

Nguyen Thai Son ◽

Dao Van Thang ◽

Tran Huy Hoang

Keyword(s):

Antibiotic Resistance ◽

Acinetobacter Baumannii ◽

Resistance Genes ◽

De Novo Assembly ◽

De Novo ◽

Antibiotic Resistance Genes ◽

Common Mechanism ◽

Genes Encoding ◽

Short Read Sequence ◽

Genome Shotgun Sequence

Acinetobacter baumannii (A. baumannii) is currently ranked as the frst concern for the development of new antibiotics due to its capacity of resistance to all available families of antibiotics. The most common mechanism of antibiotic resistance development in A. baumannii is through the acquisition of mobile genetic elements such as plasmid, transposon and integrons carrying resistance genes. A. baumannii strain TN81 was isolated from sputum specimen of a 45-year-old man at Thanh Nhan Hospital (Hanoi, Vietnam) and confrmed to be a multidrug resistance strain with high minimum inhibitory concentration value of 8/9 type of antibiotics, especially colistin. De novo assembly of the whole genome shotgun sequence of strain TN81 yielded an estimated genome size of 3,739,193 bp with 593 contigs and N50 is 9,126 bp. MLST analysis showed that TN81 belongs to ST164, which was frst reported as genome assembly in Vietnam. Resistance genes identifcation through database found that TN81 contained 12 genes encoding for antibiotic resistance. Notably, we performed de novo assembly of plasmid through short read sequence and identifed two potential plasmid-encoded antibiotic resistance genes (ant(2’’)-Ia / aadB and tet (39), which were reported for the first time as in ST164 group. This study aimed to investigate the plasmid-containing antibiotic resistance genes from a nosocomial isolate of Acinetobacter baumannii. Conclusively, all of these results would be crucial information on antibiotic resistance in A. baumannii in Vietnam.

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GENERAL PRINCIPLES OF ANTIBIOTIC RESISTANCE EVOLUTION IN BACTERIA (REVIEW OF LITERATURE)

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2020-65-6-387-393 ◽

2020 ◽

Vol 65 (6) ◽

pp. 387-393

Author(s):

N. V. Davidovich ◽

Natalya Nilolaevna Kukalevskaya ◽

E. N. Bashilova ◽

T. A. Bazhukova

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Molecular Genetic ◽

Antibiotic Resistance Genes ◽

Human Pathogens ◽

Intrinsic Resistance ◽

Resistance Evolution ◽

Genes Encoding ◽

The Impact

Currently, the impact of antibiotic resistance on human health is a worldwide problem and its study is of great interest from a molecular genetic, environmental and clinical view-point. This review summarizes the latest data about antibiotic resistance, the classification of microorganisms as sensitive and resistant to the action of antibiotics, reveals the concept of minimum inhibitory concentration from modern positions. The resistance of microorganisms to antibacterial agents can be intrinsic and acquired, as well as being one of the examples of evolution that are currently available for study. Modern methods of whole-genome sequencing and complex databases of nucleotide-tagged libraries give an idea of the multifaceted nature of the mechanisms of intrinsic resistance to antibiotics and are able to provide information on genes encoding metabolic enzymes and proteins that regulate the basic processes of the physiology of bacteria. The article describes the main ways of spreading the resistance of microorganisms, reflects the concepts of “founder effect” and the fitness cost of bacteria, which underlie the emergence and evolution of antibiotic resistance. It is shown that the origin of antibiotic resistance genes that human pathogens currently possess can be traced by studying the surrounding not only clinical, but also non-clinical (ecological) habitats. As well as microorganisms of the surrounding ecosystems are the donors of resistance genes in horizontal gene transfer.

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The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00933-15 ◽

2015 ◽

Vol 59 (10) ◽

pp. 6551-6560 ◽

Cited By ~ 90

Author(s):

Johan Bengtsson-Palme ◽

Martin Angelin ◽

Mikael Huss ◽

Sanela Kjellqvist ◽

Erik Kristiansson ◽

...

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Central Africa ◽

Antibiotic Resistance Genes ◽

Metagenomic Sequencing ◽

Content Type ◽

Exchange Programs ◽

Indian Peninsula ◽

Before And After ◽

Genes Encoding

ABSTRACTPrevious studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance ofProteobacteriain 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producingEscherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

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Forecasting the dissemination of antibiotic resistance genes across bacterial genomes

Nature Communications ◽

10.1038/s41467-021-22757-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mostafa M. H. Ellabaan ◽

Christian Munck ◽

Andreas Porse ◽

Lejla Imamovic ◽

Morten O. A. Sommer

Keyword(s):

Antibiotic Resistance ◽

Resistance Genes ◽

Antibiotic Resistance Genes ◽

Gram Negative Bacteria ◽

Bacterial Genomes ◽

Exchange Networks ◽

Gram Positive Bacteria ◽

Physiological Constraints ◽

Statistical Framework ◽

Genes Encoding

AbstractAntibiotic resistance spreads among bacteria through horizontal transfer of antibiotic resistance genes (ARGs). Here, we set out to determine predictive features of ARG transfer among bacterial clades. We use a statistical framework to identify putative horizontally transferred ARGs and the groups of bacteria that disseminate them. We identify 152 gene exchange networks containing 22,963 bacterial genomes. Analysis of ARG-surrounding sequences identify genes encoding putative mobilisation elements such as transposases and integrases that may be involved in gene transfer between genomes. Certain ARGs appear to be frequently mobilised by different mobile genetic elements. We characterise the phylogenetic reach of these mobilisation elements to predict the potential future dissemination of known ARGs. Using a separate database with 472,798 genomes from Streptococcaceae, Staphylococcaceae and Enterobacteriaceae, we confirm 34 of 94 predicted mobilisations. We explore transfer barriers beyond mobilisation and show experimentally that physiological constraints of the host can explain why specific genes are largely confined to Gram-negative bacteria although their mobile elements support dissemination to Gram-positive bacteria. Our approach may potentially enable better risk assessment of future resistance gene dissemination.

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