scholarly journals Genomics of Staphylococcus aureus ocular isolates

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0250975
Author(s):  
William L. Johnson ◽  
Michael B. Sohn ◽  
Samantha Taffner ◽  
Payel Chatterjee ◽  
Paul M. Dunman ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Vision Loss ◽  
Genomic Analysis ◽  
Valuable Insight ◽  
Ocular Tissues ◽  
Ocular Infections ◽  
Specific Strain ◽  
Sequence Types ◽  
High Throughput Manner

Staphylococcus aureus is a major cause of ocular infections, often resulting in devastating vision loss. Despite the significant morbidity associated with these infections, little is yet known regarding the specific strain types that may have a predilection for ocular tissues nor the set of virulence factors that drive its pathogenicity in this specific biological niche. Whole genome sequencing (WGS) can provide valuable insight in this regard by providing a prospective, comprehensive assessment of the strain types and virulence factors driving disease among specific subsets of clinical isolates. As such, a set of 163-member S. aureus ocular clinical strains were sequenced and assessed for both common strain types (multilocus sequence type (MLST), spa, agr) associated with ocular infections as well as the presence/absence of 235 known virulence factors in a high throughput manner. This ocular strain set was then directly compared to a fully sequenced 116-member non-ocular S. aureus strain set curated from NCBI in order to identify key differences between ocular and non-ocular S. aureus isolates. The most common sequence types found among ocular S. aureus isolates were ST5, ST8 and ST30, generally reflecting circulating non-ocular pathogenic S. aureus strains. However, importantly, ocular isolates were found to be significantly enriched for a set of enterotoxins, suggesting a potential role for this class of virulence factors in promoting ocular disease. Further genomic analysis revealed that these enterotoxins are located on mobile pathogenicity islands, thus horizontal gene transfer may promote the acquisition of enterotoxins, potentially amplifying S. aureus virulence in ocular tissues.

scholarly journals Characterisation of Staphylococcus aureus isolated from rabbits in Fujian, China

2019 ◽  
Vol 147 ◽  
Author(s):  
J. Wang ◽  
L. Sang ◽  
S. Sun ◽  
Y. Chen ◽  
D. Chen ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Antimicrobial Susceptibility ◽  
Virulence Genes ◽  
Susceptibility Test ◽  
Antimicrobial Susceptibility Test ◽  
Fujian Province ◽  
Genetic Characteristics ◽  
Resistance Rates ◽  
Sequence Types

Abstract Staphylococcus aureus has been recognised as one of the important zoonotic pathogens. However, knowledge about the epidemiology and genetic characteristics of S. aureus in rabbits was limited. The aim of this study was to determine the characteristics of 281 S. aureus isolated from dead rabbits of nine rabbit farms in Fujian Province, China. All the isolates were characterised by multi-locus sequencing typing, detection of virulence factors and antimicrobial susceptibility test. The results showed that the 281 isolates were grouped into two sequence types, ST121 (13.52%, 38/281) and ST398 (86.48%, 243/281). Surprisingly, the ST121 strains were only recovered from the lung samples from one of the nine rabbit farms studied. In the 281 isolates, the virulence genes of nuc, hla, hlb, clfA, clfB and fnbpA were positive, whereas the sea, seb, tsst, eta and etb genes were negative. Notably, the 38 ST121 isolates carried the pvl gene. All the 281 isolates were methicillin-susceptible S. aureus, and the isolates were susceptible to most of the used antibiotics, except for streptomycin, kanamycin, azithromycin and penicillin, and the resistance rates of which were 23.84%, 19.57%, 16.01% and 11.03%, respectively. This study first described the epidemiology and characteristics of S. aureus in rabbits in Fujian Province, which will help in tracking the evolution of epidemic strains and preventing the rabbit–human transmission events.

scholarly journals Genomic Analysis of Bovine Staphylococcus aureus Isolates from Milk To Elucidate Diversity and Determine the Distributions of Antimicrobial and Virulence Genes and Their Association with Mastitis

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Sohail Naushad ◽  
Diego B. Nobrega ◽  
S. Ali Naqvi ◽  
Herman W. Barkema ◽  
Jeroen De Buck
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Genes ◽  
Bovine Milk ◽  
Genomic Analysis ◽  
Whole Genome ◽  
Pathogenic Potential ◽  
Content Type ◽  
Intramammary Infections ◽  
Comprehensive Information ◽  
Sequence Types

ABSTRACT Staphylococcus aureus causes persistent clinical and subclinical bovine intramammary infections (IMI) worldwide. However, there is a lack of comprehensive information regarding genetic diversity, the presence of antimicrobial resistance (AMR), and virulence genes for S. aureus in bovine milk in Canada. Here, we performed whole-genome sequencing (WGS) of 119 Canadian bovine milk S. aureus isolates and determined they belonged to 8 sequence types (ST151, ST352, ST351, ST2187, ST2270, ST126, ST133, and ST8), 5 clonal complexes (CC151, CC97, CC126, CC133, and CC8), and 18 distinct Spa types. Pan-, core, and accessory genomes were composed of 6,340, 1,279, and 2,431 genes, respectively. Based on phenotypic screening for AMR, resistance was common against beta-lactams (19% of isolates) and sulfonamides (7% of isolates), whereas resistance against pirlimycin, tetracycline, ceftiofur, and erythromycin and to the combination of penicillin and novobiocin was uncommon (3, 3, 3, 2, and 2% of all isolates, respectively). We also determined distributions of 191 virulence factors (VFs) in 119 S. aureus isolates after classifying them into 5 functional categories (adherence [n = 28], exoenzymes [n = 21], immune evasion [n = 20], iron metabolism [n = 29], and toxins [n = 93]). Additionally, we calculated the pathogenic potential of distinct CCs and STs and determined that CC151 (ST151 and ST351) had the highest pathogenic potential (calculated by subtracting core-VFs from total VFs), followed by CC97 (ST352 and ST2187) and CC126 (ST126 and ST2270), potentially linked to their higher prevalence in bovine IMI worldwide. However, there was no statistically significant link between the presence of VF genes and mastitis. IMPORTANCE Staphylococcus aureus is a major cause of bovine intramammary infections, leading to significant economic losses to dairy industry in Canada and worldwide. There is a lack of knowledge regarding genetic diversity, the presence of antimicrobial resistance (AMR), and virulence genes for S. aureus isolated from bovine milk in Canada. Based on whole-genome sequencing and genomic analysis, we have determined the phylogeny and diversity of S. aureus in bovine milk and concluded that it had a large accessory genome, limited distribution of AMR genes, variable VF gene profiles and sequence types (ST), and clonal complex (CC)-specific pathogenic potentials. Comprehensive information on the population structure, as well as the virulence and resistance characteristics of S. aureus from bovine milk, will allow for source attribution, risk assessment, and improved therapeutic approaches in cattle.

scholarly journals Genomic Analysis of Staphylococcus aureus Isolates Associated With Peracute Non-gangrenous or Gangrenous Mastitis and Comparison With Other Mastitis-Associated Staphylococcus aureus Isolates

2021 ◽  
Vol 12 ◽  
Author(s):  
Silja Åvall-Jääskeläinen ◽  
Joanna Koort ◽  
Heli Simojoki ◽  
Suvi Taponen
Keyword(s):  
Staphylococcus Aureus ◽  
Clinical Outcome ◽  
Virulence Factors ◽  
Virulence Genes ◽  
Allelic Variation ◽  
Bovine Mastitis ◽  
Genomic Analysis ◽  
Virulence Gene ◽  
Clinical Mastitis ◽  
Comparative Genomic

Staphylococcus aureus is a highly prevalent cause of mastitis in dairy herds worldwide, capable of causing outcomes that vary from subclinical to peracute gangrenous mastitis. We performed a comparative genomic analysis between 14 isolates of S. aureus, originating from peracute bovine mastitis with very severe signs (9 gangrenous, 5 non-gangrenous) and six isolates originating from subclinical or clinical mastitis with mild to moderate signs, to find differences that could be associated with the clinical outcome of mastitis. Of the 296 virulence factors studied, 219 were detected in all isolates. No difference in the presence of virulence genes was detected between the peracute and control groups. None of the virulence factors were significantly associated with only a single study group. Most of the variation in virulence gene profiles existed between the clonal complexes. Our isolates belonged to five clonal complexes (CC97, CC133, CC151, CC479, and CC522), of which CC522 has previously been detected only in isolates originating from caprine and ovine mastitis, but not from bovine mastitis. For statistical analysis, we sorted the CCs into two groups. The group of CCs including CC133, CC479, and CC522 was associated with gangrenous mastitis, in contrast to the group of CCs including CC97 and CC151. The presence of virulence genes does not explain the clinical outcome of mastitis, but may be affected by allelic variation, and especially different regulation and thus expression in the virulence genes.

scholarly journals Analysis of the Genetic Variability of Virulence-Related Loci in Epidemic Clones of Methicillin-Resistant Staphylococcus aureus

2005 ◽  
Vol 49 (1) ◽  
pp. 366-379 ◽  
Author(s):  
A. R. Gomes ◽  
S. Vinga ◽  
M. Zavolan ◽  
H. de Lencastre
Keyword(s):  
Staphylococcus Aureus ◽  
Genetic Variability ◽  
Amino Acid Level ◽  
Point Of View ◽  
Sequence Motifs ◽  
Related Factors ◽  
Specific Sequence ◽  
Methicillin Resistant ◽  
Sequence Types ◽  
R Domain

ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) isolates have previously been classified into major epidemic clonal types by pulsed-field gel electrophoresis in combination with multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec typing. We aimed to investigate whether genetic variability in potentially polymorphic domains of virulence-related factors could provide another level of differentiation in a diverse collection of epidemic MRSA clones. The target regions of strains representative of epidemic clones and genetically related methicillin-susceptible S. aureus isolates from the 1960s that were sequenced included the R domains of clfA and clfB; the D, W, and M regions of fnbA and fnbB; and three regions in the agr operon. Sequence variation ranged from very conserved regions, such as those for RNAIII and the agr interpromoter region, to the highly polymorphic R regions of the clf genes. The sequences of the clf R domains could be grouped into six major sequence types on the basis of the sequences in their 3′ regions. Six sequence types were also observed for the fnb sequences at the amino acid level. From an evolutionary point of view, it was interesting that a small DNA stretch at the 3′ clf R-domain sequence and the fnb sequences agreed with the results of MLST for this set of strains. In particular, clfB R-domain sequences, which had a high discriminatory capacity and with which the types distinguished were congruent with those obtained by other molecular typing methods, have potential for use for the typing of S. aureus. Clone- and strain-specific sequence motifs in the clf and fnb genes may represent useful additions to a typing methodology with a DNA array.

scholarly journals 1202. Subinhibitory Concentrations of Omadacycline Inhibit Staphylococcus aureus Hemolytic Activity in Vitro

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S622-S623
Author(s):  
Alisa W Serio ◽  
S Ken Tanaka ◽  
Kelly Wright ◽  
Lynne Garrity-Ryan
Keyword(s):  
Staphylococcus Aureus ◽  
Protein Synthesis ◽  
Virulence Factors ◽  
Hemolytic Activity ◽  
Protein Biosynthesis ◽  
The United States ◽  
Aureus Strain ◽  
Protein Synthesis Inhibitors ◽  
Subinhibitory Concentrations

Abstract Background In animal models of Staphylococcus aureus infection, α-hemolysin has been shown to be a key virulence factor. Treatment of S. aureus with subinhibitory levels of protein synthesis inhibitors can decrease α-hemolysin expression. Omadacycline, a novel aminomethylcycline antibiotic in the tetracycline class of bacterial protein biosynthesis inhibitors, is approved in the United States for treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in adults. This study was performed to determine the durability of inhibition and effect of subinhibitory concentrations of omadacycline on S. aureus hemolytic activity. Methods All experiments used the methicillin-sensitive S. aureus strain Wood 46 (ATCC 10832), a laboratory strain known to secrete high levels of α-hemolysin. Minimum inhibitory concentrations (MICs) of omadacycline and comparator antibiotics (tetracycline, cephalothin, clindamycin, vancomycin, linezolid) were determined. Growth of S. aureus with all antibiotics was determined and the percentage of hemolysis assayed. “Washout” experiments were performed with omadacycline only. Results S. aureus cultures treated with 1/2 or 1/4 the MIC of omadacycline for 4 hours showed hemolysis units/108 CFU of 47% and 59% of vehicle-treated cultures, respectively (Fig. 1A, 1B). In washout experiments, treatment with as little as 1/4 the MIC of omadacycline for 1 hour decreased the hemolysis units/108 CFU by 60% for 4 hours following removal of the drug (Table 1). Figure 1 Table 1 Conclusion Omadacycline inhibited S. aureus hemolytic activity in vitro at subinhibitory concentrations and inhibition was maintained for ≥ 4 hours after removal of extracellular drug (Fig. 2). The suppression of virulence factors throughout the approved omadacycline dosing interval, in addition to the in vitro potency of omadacycline, may contribute to the efficacy of omadacycline for ABSSSI and CABP due to virulent S. aureus. This finding may apply to other organisms and other virulence factors that require new protein synthesis to establish disease. Figure 2 Disclosures Alisa W. Serio, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) S. Ken Tanaka, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Kelly Wright, PharmD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Lynne Garrity-Ryan, PhD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder)

scholarly journals Characterization and Genome Analysis of Staphylococcus aureus Podovirus CSA13 and Its Anti-Biofilm Capacity

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 54 ◽  
Author(s):  
Yoyeon Cha ◽  
Jihwan Chun ◽  
Bokyung Son ◽  
Sangryeol Ryu
Keyword(s):  
Staphylococcus Aureus ◽  
Biocontrol Agent ◽  
Genomic Analysis ◽  
Open Reading Frames ◽  
Experimental Setting ◽  
Human Pathogens ◽  
Bacteriophage Therapy ◽  
Chromosomal Structure ◽  
Inhibition Effect ◽  
Reading Frames

Staphylococcus aureus is one of the notable human pathogens that can be easily encountered in both dietary and clinical surroundings. Among various countermeasures, bacteriophage therapy is recognized as an alternative method for resolving the issue of antibiotic resistance. In the current study, bacteriophage CSA13 was isolated from a chicken, and subsequently, its morphology, physiology, and genomics were characterized. This Podoviridae phage displayed an extended host inhibition effect of up to 23 hours of persistence. Its broad host spectrum included methicillin susceptible S. aureus (MSSA), methicillin resistant S. aureus (MRSA), local S. aureus isolates, as well as non-aureus staphylococci strains. Moreover, phage CSA13 could successfully remove over 78% and 93% of MSSA and MRSA biofilms in an experimental setting, respectively. Genomic analysis revealed a 17,034 bp chromosome containing 18 predicted open reading frames (ORFs) without tRNAs, representing a typical chromosomal structure of the staphylococcal Podoviridae family. The results presented here suggest that phage CSA13 can be applicable as an effective biocontrol agent against S. aureus.

scholarly journals Phosphorylation of MgrA and Its Effect on Expression of the NorA and NorB Efflux Pumps of Staphylococcus aureus

2010 ◽  
Vol 192 (10) ◽  
pp. 2525-2534 ◽  
Author(s):  
Que Chi Truong-Bolduc ◽  
David C. Hooper
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistance ◽  
Virulence Factors ◽  
Double Mutant ◽  
Efflux Pumps ◽  
Efflux Transporters ◽  
Global Regulator ◽  
Binding Assays ◽  
Genes Encoding ◽  
Gel Shift

ABSTRACT MgrA is a global regulator in Staphylococcus aureus that controls the expression of diverse genes encoding virulence factors and multidrug resistance (MDR) efflux transporters. We identified pknB, which encodes the (Ser/Thr) kinase PknB, in the S. aureus genome. PknB was able to autophosphorylate as well as phosphorylate purified MgrA. We demonstrated that rsbU, which encodes a Ser/Thr phosphatase and is involved in the activation of the SigB regulon, was able to dephosphorylate MgrA-P but not PknB-P. Serines 110 and 113 of MgrA were found to be phosphorylated, and Ala substitutions at these positions resulted in reductions in the level of phosphorylation of MgrA. DNA gel shift binding assays using norA and norB promoters showed that MgrA-P was able to bind the norB promoter but not the norA promoter, a pattern which was the reverse of that for unphosphorylated MgrA. The double mutant MgrAS110A-S113A bound to the norA promoter but not the norB promoter. The double mutant led to a 2-fold decrease in norA transcripts and a 2-fold decrease in the MICs of norfloxacin and ciprofloxacin in strain RN6390. Thus, phosphorylation of MgrA results in loss of binding to the norA promoter, but with a gain of the ability to bind the norB promoter. Loss of the ability to phosphorylate MgrA by Ala substitution resulted in increased repression of norA expression and in reductions in susceptibilities to NorA substrates.

New Strategies Targeting Virulence Factors of Staphylococcus aureus and Pseudomonas aeruginosa

2017 ◽  
Vol 38 (03) ◽  
pp. 346-358 ◽  
Author(s):  
Bruno François ◽  
Charles-Edouard Luyt ◽  
C. Stover ◽  
Jeffery Brubaker ◽  
Jean Chastre ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Effective Utilization ◽  
Mechanically Ventilated ◽  
Stage Of Development ◽  
Antivirulence Agents ◽  
Interventional Therapies ◽  
Improve Patient ◽  
New Strategies

AbstractMorbidity, mortality, and economic burden of nosocomial pneumonia caused by Staphylococcus aureus and Pseudomonas aeruginosa remain high in mechanically ventilated and hospitalized patients despite the use of empirical antibiotic therapy or antibiotics against specific classes of pathogens and procedures to reduce nosocomial infections in hospital settings. Newer agents that neutralize or inhibit specific S. aureus or P. aeruginosa virulence factors may eliminate or reduce the risk for developing pneumonia before or during mechanical ventilation and may improve patient outcomes through mechanisms that differ from those of antibiotics. In this article, we review the types, mechanisms of action, potential advantages, and stage of development of antivirulence agents (AVAs) that hold promise as alternative preventive or interventional therapies against S. aureus– and P. aeruginosa–associated nosocomial pneumonias. We also present and discuss challenges to the effective utilization of AVAs separately from or in addition to antibiotics and the design of clinical trials and meaningful study end points.

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