scholarly journals Massive genome decay and expansion of insertion sequences drive the evolution of a novel host-restricted bacterial pathogen

2020 ◽  
Author(s):  
Gonzalo Yebra ◽  
Andreas F Haag ◽  
Maan M Neamah ◽  
Bryan A Wee ◽  
Emily J Richardson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Relatedness ◽  
Bacterial Species ◽  
Small Ruminants ◽  
Bacterial Pathogen ◽  
Insertion Sequences ◽  
Evolutionary Trajectory ◽  
Intergenic Regions ◽  
Genome Decay ◽  
Novel Concept

AbstractBackgroundThe emergence of new bacterial pathogens represents a major threat to public and veterinary health. Staphylococcus aureus is a multi-host bacterial species comprising pathogenic clones with distinct tropisms for human and livestock species. A S. aureus microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for outbreaks of a specific lymphadenitis pathology (Morel’s disease) exclusively found in small ruminants. However, the evolutionary history of S. aureus subsp. anaerobius and its genetic relatedness to S. aureus are unknown.ResultsEvolutionary genomic analyses of clinical S. aureus subsp. anaerobius isolates sampled across 3 decades revealed this clone emerged from a S. aureus progenitor about 1000 years ago (95%CI: 716-1184), before differentiating into two distinct lineages representing African (emerged in 1930 [1907-1951)) and European (1777 [1716-1832]) isolates. S. aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to a highly niche-specific pathogen of small ruminant lymph nodes involved acquisition of a pathogenicity island encoding an effector with ruminant host-specificity, large genomic rearrangements, and the accumulation of at least 205 pseudogenes resulting in a highly fastidious metabolism underpinning its restricted ecological niche. Importantly, acquisition and expansion of ~87 insertion sequences located in conserved intergenic regions provided distinct mechanisms for the control of expression of flanking genes, representing a novel concept of transcriptional regulon.ConclusionsOur findings provide a remarkable example of the evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodelling of the S. aureus genome.

scholarly journals Radical genome remodelling accompanied the emergence of a novel host-restricted bacterial pathogen

2021 ◽  
Vol 17 (5) ◽  
pp. e1009606
Author(s):  
Gonzalo Yebra ◽  
Andreas F. Haag ◽  
Maan M. Neamah ◽  
Bryan A. Wee ◽  
Emily J. Richardson ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Evolutionary Trajectory ◽  
Ancestral Gene ◽  
Genomic Analyses ◽  
Specific Effector ◽  
Novel Host ◽  
Intergenic Regions ◽  
History Of

The emergence of new pathogens is a major threat to public and veterinary health. Changes in bacterial habitat such as a switch in host or disease tropism are typically accompanied by genetic diversification. Staphylococcus aureus is a multi-host bacterial species associated with human and livestock infections. A microaerophilic subspecies, Staphylococcus aureus subsp. anaerobius, is responsible for Morel’s disease, a lymphadenitis restricted to sheep and goats. However, the evolutionary history of S. aureus subsp. anaerobius and its relatedness to S. aureus are unknown. Population genomic analyses of clinical S. aureus subsp. anaerobius isolates revealed a highly conserved clone that descended from a S. aureus progenitor about 1000 years ago before differentiating into distinct lineages that contain African and European isolates. S. aureus subsp. anaerobius has undergone limited clonal expansion, with a restricted population size, and an evolutionary rate 10-fold slower than S. aureus. The transition to its current restricted ecological niche involved acquisition of a pathogenicity island encoding a ruminant host-specific effector of abscess formation, large chromosomal re-arrangements, and the accumulation of at least 205 pseudogenes, resulting in a highly fastidious metabolism. Importantly, expansion of ~87 insertion sequences (IS) located largely in intergenic regions provided distinct mechanisms for the control of expression of flanking genes, including a novel mechanism associated with IS-mediated anti-anti-sense decoupling of ancestral gene repression. Our findings reveal the remarkable evolutionary trajectory of a host-restricted bacterial pathogen that resulted from extensive remodelling of the S. aureus genome through an array of diverse mechanisms in parallel.

scholarly journals Staphylococcus aureus Isolated from Ruminants with Mastitis in Northern Greece Dairy Herds: Genetic Relatedness and Phenotypic and Genotypic Characterization

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 176
Author(s):  
Charalampos Kotzamanidis ◽  
George Vafeas ◽  
Virginia Giantzi ◽  
Sofia Anastasiadou ◽  
Stavros Mygdalias ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Genetic Relatedness ◽  
Multiple Correspondence Analysis ◽  
Small Ruminants ◽  
Northern Greece ◽  
Spa Typing ◽  
Diverse Range ◽  
Geographical Regions ◽  
Genotypic Analysis

Staphylococcus aureus is the most common mastitis-related pathogen in dairy cattle, goats, and sheep worldwide. However, the population structure and genomic characteristics of mastitis-associated S. aureus in small ruminants are limited. Furthermore, the genotypic and phenotypic characteristics involved in the pathogenicity of S. aureus have been thoroughly defined, yet their association with the severity of mastitis is not fully established. Here, we performed genotyping by pulsed-field gel electrophoresis (PFGE) and spa analyses to assess the genetic diversity and relatedness of 162 S. aureus strains recovered from clinical mastitis (CM) and subclinical mastitis (SCM) cases from goats, sheep, and bovines. PFGE analysis revealed 108 distinguishable pulsotypes and 3 main clusters that comprised isolates from the three host species, while according to spa typing, 32 different spa types were identified. Genotypic analysis revealed a spreading of genetically related or indistinguishable S. aureus strains among ovine, caprine, and bovine farms of distant geographical regions. In total, 28 different staphylococcal enterotoxin (SE) gene profiles were observed, revealing a diverse range of SE genes among isolates. By evaluating the antimicrobial resistance, we found low phenotypic antimicrobial resistance among all ruminant isolates. We also performed multiple correspondence analysis, which indicated that the presence of the sec gene, biofilm production, and high autoaggregation ability are associated with CM cases.

scholarly journals Fitness Cost Evolution of Natural Plasmids of Staphylococcus aureus

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pedro Dorado-Morales ◽  
M. Pilar Garcillán-Barcia ◽  
Iñigo Lasa ◽  
Cristina Solano
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Bacterial Pathogen ◽  
Fitness Cost ◽  
High Rate ◽  
Insertion Sequences ◽  
New Host ◽  
Content Type ◽  
Antimicrobial Resistance Genes

ABSTRACT Plasmids have largely contributed to the spread of antimicrobial resistance genes among Staphylococcus strains. Knowledge about the fitness cost that plasmids confer on clinical staphylococcal isolates and the coevolutionary dynamics that drive plasmid maintenance is still scarce. In this study, we aimed to analyze the initial fitness cost of plasmids in the bacterial pathogen Staphylococcus aureus and the plasmid-host adaptations that occur over time. For that, we first designed a CRISPR (clustered regularly interspaced palindromic repeats)-based tool that enables the removal of native S. aureus plasmids and then transferred three different plasmids isolated from clinical S. aureus strains to the same-background clinical cured strain. One of the plasmids, pUR2940, obtained from a livestock-associated methicillin-resistant S. aureus (LA-MRSA) ST398 strain, imposed a significant fitness cost on both its native and the new host. Experimental evolution in a nonselective medium resulted in a high rate pUR2940 loss and selected for clones with an alleviated fitness cost in which compensatory adaptation occurred via deletion of a 12.8-kb plasmid fragment, contained between two ISSau10 insertion sequences and harboring several antimicrobial resistance genes. Overall, our results describe the relevance of plasmid-borne insertion sequences in plasmid rearrangement and maintenance and suggest the potential benefits of reducing the use of antibiotics both in animal and clinical settings for the loss of clinical multidrug resistance plasmids. IMPORTANCE Plasmids are major agents in the spread of antibiotic resistance genes among bacteria. How plasmids and their hosts coevolve to reduce the fitness cost associated with plasmid carriage when bacteria grow in an antibiotic-free environment is not well understood. Here, we investigated the cost and the genetic adaptations that occur during evolution in the absence of antibiotics when the bacterial pathogen Staphylococcus aureus acquires a new plasmid. Our results show the occurrence, at the end of evolution, of plasmid rearrangements mediated by insertion sequences that lead to the loss of antimicrobial resistance genes from the plasmid and an alleviated fitness cost. Our results thus highlight the probable benefits of reducing the use of antibiotics in management programs for the selection of S. aureus clones carrying plasmids that no longer confer resistance.

scholarly journals Genome-Wide Identification of Resveratrol Intrinsic Resistance Determinants in Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 82
Author(s):  
Liping Liu ◽  
Hanne Ingmer ◽  
Martin Vestergaard
Keyword(s):  
Staphylococcus Aureus ◽  
Stress Response ◽  
Inhibitory Activity ◽  
Bacterial Species ◽  
Dna Integrity ◽  
Intrinsic Resistance ◽  
Potential Health ◽  
Cellular Effects ◽  
Development Of Resistance ◽  
Wide Range

Resveratrol has been extensively studied due to its potential health benefits in multiple diseases, for example, cancer, obesity and cardiovascular diseases. Besides these properties, resveratrol displays inhibitory activity against a wide range of bacterial species; however, the cellular effects of resveratrol in bacteria remain incompletely understood, especially in the human pathogen, Staphylococcus aureus. In this study, we aimed to identify intrinsic resistance genes that aid S. aureus in tolerating the activity of resveratrol. We screened the Nebraska Transposon Mutant Library, consisting of 1920 mutants with inactivation of non-essential genes in S. aureus JE2, for increased susceptibly to resveratrol. On agar plates containing 0.5× the minimum inhibitory concentration (MIC), 17 transposon mutants failed to grow. Of these, four mutants showed a two-fold reduction in MIC, being the clpP protease mutant and three mutants with deficiencies in the electron transport chain (menD, hemB, aroC). The remaining 13 mutants did not show a reduction in MIC, but were confirmed by spot-assays to have increased susceptibility to resveratrol. Several genes were associated with DNA damage repair (recJ, xerC and xseA). Treatment of S. aureus JE2 with sub-inhibitory concentrations of resveratrol did not affect the expression of recJ, xerC and xseA, but increased expression of the SOS–stress response genes lexA and recA, suggesting that resveratrol interferes with DNA integrity in S. aureus. Expression of error-prone DNA polymerases are part of the SOS–stress response and we could show that sub-inhibitory concentrations of resveratrol increased overall mutation frequency as measured by formation of rifampicin resistant mutants. Our data show that DNA repair systems are important determinants aiding S. aureus to overcome the inhibitory activity of resveratrol. Activation of the SOS response by resveratrol could potentially facilitate the development of resistance towards conventional antibiotics in S. aureus.

scholarly journals Moraxella catarrhalis: from Emerging to Established Pathogen

2002 ◽  
Vol 15 (1) ◽  
pp. 125-144 ◽  
Author(s):  
Cees M. Verduin ◽  
Cees Hol ◽  
André Fleer ◽  
Hans van Dijk ◽  
Alex van Belkum
Keyword(s):  
Moraxella Catarrhalis ◽  
Current Knowledge ◽  
Bacterial Species ◽  
Bacterial Pathogen ◽  
Diagnostic Techniques ◽  
Human Infection ◽  
Molecular Diagnostic ◽  
Molecular Diagnostic Techniques ◽  
Pathogenic Potential ◽  
The Past

SUMMARY Moraxella catarrhalis (formerly known as Branhamella catarrhalis) has emerged as a significant bacterial pathogen of humans over the past two decades. During this period, microbiological and molecular diagnostic techniques have been developed and improved for M. catarrhalis, allowing the adequate determination and taxonomic positioning of this pathogen. Over the same period, studies have revealed its involvement in respiratory (e.g., sinusitis, otitis media, bronchitis, and pneumonia) and ocular infections in children and in laryngitis, bronchitis, and pneumonia in adults. The development of (molecular) epidemiological tools has enabled the national and international distribution of M. catarrhalis strains to be established, and has allowed the monitoring of nosocomial infections and the dynamics of carriage. Indeed, such monitoring has revealed an increasing number of Β-lactamase-positive M. catarrhalis isolates (now well above 90%), underscoring the pathogenic potential of this organism. Although a number of putative M. catarrhalis virulence factors have been identified and described in detail, their relationship to actual bacterial adhesion, invasion, complement resistance, etc. (and ultimately their role in infection and immunity), has been established in a only few cases. In the past 10 years, various animal models for the study of M. catarrhalis pathogenicity have been described, although not all of these models are equally suitable for the study of human infection. Techniques involving the molecular manipulation of M. catarrhalis genes and antigens are also advancing our knowledge of the host response to and pathogenesis of this bacterial species in humans, as well as providing insights into possible vaccine candidates. This review aims to outline our current knowledge of M. catarrhalis, an organism that has evolved from an emerging to a well-established human pathogen.

scholarly journals Prevalence and Genetic Relatedness of Methicillin-Susceptible Staphylococcus aureus Isolates Detected by the Xpert MRSA Nasal Assay

2011 ◽  
Vol 49 (8) ◽  
pp. 2996-2999 ◽  
Author(s):  
S. S. Arbefeville ◽  
K. Zhang ◽  
J. S. Kroeger ◽  
W. J. Howard ◽  
D. J. Diekema ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Relatedness

scholarly journals No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

2021 ◽  
Vol 9 (2) ◽  
pp. 244
Author(s):  
Vishal Gor ◽  
Ryosuke L. Ohniwa ◽  
Kazuya Morikawa
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
High Frequency ◽  
Direct Evidence ◽  
Bacterial Species ◽  
Phase Variation ◽  
Opportunistic Pathogen ◽  
Adaptation Strategy ◽  
Innate Immune ◽  
Epigenetic Mechanisms

Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field.

scholarly journals Identification and antibiogram study of bacterial species isolated from milk samples of different locations in Bangladesh

2016 ◽  
Vol 1 (3) ◽  
pp. 457-462 ◽  
Author(s):  
Md Nuruzzaman Munsi ◽  
Nathu Ram Sarker ◽  
Razia Khatun ◽  
Mohammed Khorshed Alam
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Salmonella Typhi ◽  
Diffusion Method ◽  
Biochemical Tests ◽  
Public Health Importance ◽  
Milk Samples ◽  
First Choice

Cow’s milk containing pathogenic bacteria is an important threat to the consumers. The objectives of the present study were to identify the bacterial agents of public health importance in milk samples (n=35) of different locations and to determine their sensitivity to different antibiotics. The milk samples were collected and transported aseptically and subsequently allowed for culture in bacteriological media, Gram’s staining and biochemical tests for the identification of bacterial species. The bacteria identified were Staphylococcus aureus, Escherichia coli and Salmonella typhi, and their prevalence, in case of vendor milk specimens (n=28), were 96.43%, 53.57% and 35.71% respectively, and of brand milk specimens (n=7), were 42.86 %, 28.57% and 0%, respectively. This suggests that cautionary measures should be taken for quality milk production and consumption. The antibiotic sensitivity test was done by disc diffusion method and the average inhibition zones, in case of Staphylococcus aureus, were 32 mm for oxytetracycline, 26 mm for amoxicillin, 35 mm for ciprofloxacin, 27 mm for cefotaxime, 30 mm for ceftriaxone, 30 mm for azithromycin, and 26 mm for erythromycin; in case of Escherichia coli, were 5 mm for oxytetracycline, 9 mm for amoxicillin, 22 mm for ciprofloxacin, 30 mm for cefotaxime, 31 mm for ceftriaxone, 15 mm for azithromycin, and 0 mm for erythromycin; in case of Salmonella typhi., were 25 mm for oxytetracycline, 24 mm for amoxicillin, 38 mm for ciprofloxacin, 31 mm for cefotaxime, 34 mm for ceftriaxone, 24 mm for azithromycin, and 0 mm for erythromycin. Therefore, ciprofloxacin and ceftriaxone may be the antibiotics of first choice, and cefotaxime and azithromycin may be the second choice among the test antibiotics for the treatment of illness caused by these bacteria.Asian J. Med. Biol. Res. December 2015, 1(3): 457-462

scholarly journals Crystal structure of the ribonuclease-P-protein subunit from Staphylococcus aureus

2018 ◽  
Vol 74 (10) ◽  
pp. 632-637
Author(s):  
Lisha Ha ◽  
Jennifer Colquhoun ◽  
Nicholas Noinaj ◽  
Chittaranjan Das ◽  
Paul M. Dunman ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Staphylococcus Aureus ◽  
Rna Processing ◽  
Bacterial Species ◽  
Rna Degradation ◽  
Ribonuclease P ◽  
Protein Subunit ◽  
Aromatic Residues ◽  
Cellular Processes ◽  
P Protein

Staphylococcus aureus ribonuclease-P-protein subunit (RnpA) is a promising antimicrobial target that is a key protein component for two essential cellular processes, RNA degradation and transfer-RNA (tRNA) maturation. The first crystal structure of RnpA from the pathogenic bacterial species, S. aureus, is reported at 2.0 Å resolution. The structure presented maintains key similarities with previously reported RnpA structures from bacteria and archaea, including the highly conserved RNR-box region and aromatic residues in the precursor-tRNA 5′-leader-binding domain. This structure will be instrumental in the pursuit of structure-based designed inhibitors targeting RnpA-mediated RNA processing as a novel therapeutic approach for treating S. aureus infections.

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