scholarly journals Atypical Presentation of Methicillin-Susceptible Staphylococcus aureus Infection in a Dengue-Positive Patient: A Case Report with Virulence Genes Analysis

Pathogens ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 190
Author(s):  
Soo Tein Ngoi ◽  
Yee Wan Lee ◽  
Wen Kiong Niek ◽  
Foong Kee Kan ◽  
Sazaly AbuBakar ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Dengue Fever ◽  
Genomic Sequence ◽  
Protein A ◽  
Mortality And Morbidity ◽  
Multiple Organs ◽  
Patient Reported ◽  
Mssa Strain ◽  
Genes Encoding ◽  
Staphylococcal Pneumonia

Concurrent bacteraemia in patients with dengue fever is rarely reported. We report a case of a patient who initially presented with symptoms typical of dengue fever but later succumbed to septic shock caused by hypervirulent methicillin-susceptible Staphylococcus aureus (MSSA). A 50-year-old female patient with hypertension and diabetes mellitus presented with typical symptoms of dengue fever. Upon investigation, the patient reported having prolonged fever for four days prior to hospitalization. Within 24 hours post-admission, the patient developed pneumonia and refractory shock, and ultimately succumbed to multiple-organs failure. Microbiological examination of the blood culture retrieved a pan susceptible MSSA strain. Genomic sequence analyses of the MSSA strain identified genes encoding staphylococcal superantigens (enterotoxin staphylococcal enterotoxin C 3 (SEC3) and enterotoxin-like staphylococcal enterotoxins-like toxin L (SElL)) that have been associated with toxic shock syndrome in human hosts. Genes encoding important toxins (Panton-Valentine leukocidins, alpha-haemolysin, protein A) involved in the development of staphylococcal pneumonia were also present in the MSSA genome. Staphylococcus aureus co-infections in dengue are uncommon but could be exceptionally fatal if caused by a toxin-producing strain. Clinicians should be aware of the risks and signs of sepsis in dengue fever, thus allowing early diagnosis and starting of antibiotic treatment in time to lower the mortality and morbidity rates.

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

2020 ◽  
Vol 295 (32) ◽  
pp. 10870-10884 ◽  
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.

scholarly journals Prevalence and Molecular Characterization of Enterotoxin-Producing Strains of Staphylococcus Aureus Isolated from Serbian Dairy Cows

2016 ◽  
Vol 66 (4) ◽  
pp. 466-477 ◽  
Author(s):  
Marija Pajić ◽  
Stanko Boboš ◽  
Branko Velebit ◽  
Zoran Rašić ◽  
Vera Katić ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Protein A ◽  
Food Poisoning ◽  
Clinical Mastitis ◽  
Staphylococcal Protein A ◽  
Phylogenetic Groups ◽  
Gene Encoding ◽  
Staphylococcal Enterotoxins ◽  
Genes Encoding ◽  
The Republic

AbstractStaphylococcus aureus is known worldwide as a frequent cause of mastitis in dairy cattle. Due to the production of heath resistant enterotoxins, this pathogen is also a major cause of food poisoning among humans, with symptoms of often severe vomiting and diarrhea. The aim of our study was to determine the prevalence of enterotoxinproducing strains of S. aureus originating from samples of cows with subclinical and clinical mastitis in the Republic of Serbia. Furthermore, we analyzed the type of staphylococcal enterotoxin they produce and phylogenetic relatedness among the S. aureus isolates recovered from milk in this study. Production of staphylococcal enterotoxins A, B, C, D and E was determined by commercial immunoenzyme assay VIDAS® SET2, and presence of corresponding genes encoding enterotoxin synthesis in positive isolates confi rmed by Polymerase Chain Reaction. Enterotoxin production was determined in 5 out of 75 (6.67%) isolates of S. aureus and all of them produced staphylococcal enterotoxins C. After analyzing the nucleotide sequence of the gene encoding the synthesis of staphylococcal protein A, S. aureus isolates were assigned into 2 phylogenetic groups, including 7 clusters. All S. aureus isolates with the presence of sec gene formed one cluster even dough they originated from milk samples from different farms.

scholarly journals Presence of egc-positive major clones ST 45, 30 and 22 among methicillin-resistant and methicillin-susceptible oral Staphylococcus aureus strains

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ewa Kwapisz ◽  
Katarzyna Garbacz ◽  
Maja Kosecka-Strojek ◽  
Justyna Schubert ◽  
Jacek Bania ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Oral Cavity ◽  
Protein A ◽  
Methicillin Resistant ◽  
Dental Patients ◽  
Genes Encoding ◽  
Clonal Distribution ◽  
Toxic Shock Syndrome Toxin ◽  
Mrsa Strains ◽  
Resistance Rates

Abstract The oral cavity may comprise a significant reservoir for Staphylococcus aureus but the data on molecular epidemiology and clonal distribution of oral strains are really scarce. This study aimed to evaluate the clonal relatedness in S. aureus isolated from oral cavity and their relationship with carriage of virulence genes, and antimicrobial resistance profiles. A total of 139 oral S. aureus isolates were obtained from 2327 analysed oral samples of dental patients. Antimicrobial susceptibility testing was performed. Isolates were characterized using protein A gene (spa) typing, spa-CC clonal complexes, toxin genes and SCCmec typing for MRSA. High resistance rates for penicillin, tetracycline and gentamicin were detected, respectively 58.3%, 42.4%, and 35.2%. Twelve (8.6%) S. aureus isolates were identified as MRSA. All of MRSA isolates were mecA-positive and mecC-negative. SCCmec IV was the most common type (66.7%), which was typical for community-acquired MRSA (CA-MRSA). Overall, the enterotoxin gene cluster (egc) was the most frequent detected virulence factor (44.9%), both in MSSA and MRSA isolates. Presence of genes encoding for the enterotoxins (sea, seb, sec, seh, sek), exfoliative toxin A (eta), and toxic shock syndrome toxin-1 (tst) was also observed. Strains carrying lukS-PV/lukF-PV genes belonged to SCCmecV- spa type t437. The most prevalent spa types were t091, t015, t084, t002, t571, and t026 among all 57 identified. Spa types, including 3 new ones, grouped in 6 different spa-CC clonal complexes, with four major dominated; CC45, CC30, CC5, and CC15. This study demonstrated that both methicillin-susceptible and methicillin-resistant major European clones of S. aureus could be isolated from the oral cavity of dental patients, with the emergence of PVL-positive CA-MRSA strains. The oral cavity should be considered as a possible source of toxigenic egc-positive S. aureus strains, in terms of potential risk of cross-infection and dissemination to other body sites.

Genetic characterization of staphopain genes in Staphylococcus aureus

2004 ◽  
Vol 385 (11) ◽  
pp. 1059-1067 ◽  
Author(s):  
Ewa Golonka ◽  
Renata Filipek ◽  
Artur Sabat ◽  
Anna Sinczak ◽  
Jan Potempa
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Genomic Sequence ◽  
Sequence Data ◽  
Proteolytic Enzymes ◽  
Disease Process ◽  
Pcr Amplification ◽  
Single Copy ◽  
Pcr Rflp ◽  
Genes Encoding

AbstractStaphylococcus aureus, a leading cause of bacterial infections in humans, is endowed with a wealth of virulence factors that contribute to the disease process. Several extracellular proteolytic enzymes, including cysteine proteinases referred to as the staphopains (staphopain A, encoded by thescpAgene, and staphopain B, encoded bysspB), have proposed roles for staphylococcal virulence. Here we present data regarding the distribution, copy number and genetic variability of the genes encoding the staphopains in a large number ofS. aureusstrains. The polymorphism of thescpAandsspBgenes in three laboratory strains and 126 clinical isolates was analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). Both genes were detected in all isolates by PCR amplification and, based on the PCR-RFLP patterns, classified as four types forscpAand six types forsspB. Those with the most divergent patterns were subjected to DNA sequencing and compared with genomic sequence data for the seven available strains ofS. aureus. Southern blot analysis of thescpAandsspBsequences indicates that they are strongly conserved as single-copy genes in the genome of eachS. aureusstrain investigated. Taken together, these data suggest that the staphopains have important housekeeping and/or virulence functions, and therefore may constitute an interesting target for the development of therapeutic inhibitors for the treatment of staphylococcal diseases.

scholarly journals Analysis of genomic diversity within the Xr-region of the protein A gene in clinical isolates of Staphylococcus aureus

1999 ◽  
Vol 122 (2) ◽  
pp. 241-249 ◽  
Author(s):  
N. KOBAYASHI ◽  
S. URASAWA ◽  
N. UEHARA ◽  
N. WATANABE
Keyword(s):  
Staphylococcus Aureus ◽  
Repeat Unit ◽  
Protein A ◽  
Genomic Diversity ◽  
Clinical Isolates ◽  
Nucleotide Sequence Analysis ◽  
Repeat Units ◽  
Multiple Protein ◽  
Genes Encoding ◽  
Genetic Clusters

Protein A of Staphylococcus aureus contains a polymorphic Xr-region characterized by a tandem repeat of eight amino acid units. In this study, the diversity of genes encoding the repeat regions and their relatedness among S. aureus strains was analyzed. Ten different protein-A types characterized by repeat numbers 4–13 were identified in a total of 293 clinical isolates. The protein-A type with 10 repeat units (10 repeats) in the Xr-region was most frequently detected in methicillin-resistant S. aureus, whereas the majority of methicillin- susceptible strains were distributed almost evenly into protein-A types with 7–11 repeats. Strains that belonged to a single coagulase type were classified into multiple protein-A types, e.g. strains with the common coagulase types II and VII were differentiated into 7 and 8 protein-A types, respectively.Nucleotide sequence analysis of the Xr-region of 42 representative strains revealed the presence of 37 different genotypes (spa types), which were constituted by a combination of several of 24 different repeat unit genotypes. Based on the similarity in arrangement of repeat unit genotypes, 34 strains with different repeat numbers were classified into 5 genetic clusters (C1–C5). The clusters C1, C2 and C3 consisted exclusively of strains with identical coagulase types II, III, and IV, respectively. These findings suggested that the protein-A gene of S. aureus has evolved from a common ancestral clone in individual clusters independently.

scholarly journals Regulation of agr-Dependent Virulence Genes in Staphylococcus aureus by RNAIII from Coagulase-Negative Staphylococci

1998 ◽  
Vol 180 (12) ◽  
pp. 3181-3186 ◽  
Author(s):  
Karin Tegmark ◽  
Eva Morfeldt ◽  
Staffan Arvidson
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Surface ◽  
Serine Protease ◽  
Protein A ◽  
Surface Proteins ◽  
Open Reading Frames ◽  
Alpha Toxin ◽  
Coagulase Negative Staphylococci ◽  
Cell Surface Proteins ◽  
Genes Encoding

ABSTRACT Many of the genes coding for extracellular toxins, enzymes, and cell surface proteins in Staphylococcus aureus are regulated by a 510-nucleotide (nt) RNA molecule, RNAIII. Transcription of genes encoding secreted toxins and enzymes, includinghla (alpha-toxin), saeB (enterotoxin B),tst (toxic shock syndrome toxin 1), and ssp(serine protease), is stimulated, while transcription of genes encoding cell surface proteins, like spa (protein A) andfnb (fibronectin binding proteins), is repressed. Besides being a regulator, RNAIII is also an mRNA coding for staphylococcal delta-lysin. We have identified RNAIII homologs in three different coagulase-negative staphylococci (CoNS), i.e., Staphylococcus epidermidis, Staphylococcus simulans, andStaphylococcus warneri. RNAIII from these CoNS turned out to be very similar to that of S. aureus and contained open reading frames encoding delta-lysin homologs. Though a number of big insertions and/or deletions have occurred, mainly in the 5′ half of the molecules, the sequences show a high degree of identity, especially in the first 50 and last 150 nt. The CoNS RNAIII had the ability to completely repress transcription of protein A in an RNAIII-deficientS. aureus mutant and the ability to stimulate transcription of the alpha-toxin and serine protease genes. However, the stimulatory effect was impaired compared to that of S. aureus RNAIII, suggesting that these regulatory functions are independent. By creating S. epidermidis-S. aureus RNAIII hybrids, we could also show that both the 5′ and 3′ halves of the RNAIII molecule are involved in the transcriptional regulation of alpha-toxin and serine protease mRNAs in S. aureus.

scholarly journals Identification and characterization of msa (SA1233), a gene involved in expression of SarA and several virulence factors in Staphylococcus aureus

Microbiology ◽  
2006 ◽  
Vol 152 (9) ◽  
pp. 2559-2572 ◽  
Author(s):  
Karthik Sambanthamoorthy ◽  
Mark S. Smeltzer ◽  
Mohamed O. Elasri
Keyword(s):  
Staphylococcus Aureus ◽  
Virulence Factors ◽  
Protein A ◽  
Laboratory Strain ◽  
Reporter System ◽  
Accessory Gene ◽  
Accessory Gene Regulator ◽  
Genes Encoding ◽  
Membrane Spanning ◽  
The Impact

The staphylococcal accessory regulator (sarA) plays a central role in the regulation of virulence in Staphylococcus aureus. To date, studies involving sarA have focused on its activity as a global regulator that modulates transcription of a wide variety of genes (>100) and its role in virulence. However, there is also evidence to suggest the existence of accessory elements that modulate SarA production and/or function. A reporter system was developed to identify such elements, and a new gene, msa (SA1233), mutation of which results in reduced expression of SarA, was identified and characterized. Additionally, it was shown that mutation of msa resulted in altered transcription of the accessory gene regulator (agr) and the genes encoding several virulence factors including alpha toxin (hla) and protein A (spa). However, the impact of mutating msa was different in the laboratory strain RN6390 and the clinical isolate UAMS-1. For instance, mutation of msa caused a decrease in spa and hla transcription in RN6390 but had a different effect in UAMS-1. The strain-dependent effects of the msa mutation were similar to those observed previously, which suggests that msa may modulate the production of specific virulence factors through its impact on sarA. Interestingly, sequence analysis of Msa suggests that it is a putative membrane protein with three membrane-spanning regions, indicating that Msa might interact with the environment. The findings show that msa is involved in the expression of SarA and several virulence factors.

scholarly journals Emergence of a Staphylococcus aureus Clone Resistant to Mupirocin and Fusidic Acid Carrying Exotoxin Genes and Causing Mainly Skin Infections

2017 ◽  
Vol 55 (8) ◽  
pp. 2529-2537 ◽  
Author(s):  
Anastassios Doudoulakakis ◽  
Iris Spiliopoulou ◽  
Nikolaos Spyridis ◽  
Nikolaos Giormezis ◽  
John Kopsidas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Fusidic Acid ◽  
Protein A ◽  
Acid Resistance ◽  
Content Type ◽  
Staphylococcal Infections ◽  
Genes Encoding ◽  
Topical Antimicrobials ◽  
Resistant Strains ◽  
High Level

ABSTRACTSkin and soft tissue infections (SSTIs) caused by mupirocin-resistantStaphylococcus aureusstrains have recently increased in number in our settings. We sought to evaluate the characteristics of these cases over a 43-month period. Data for all community-acquired staphylococcal infections caused by mupirocin-resistant strains were retrospectively reviewed. Genes encoding products producing high-level resistance (HLR) to mupirocin (mupA), fusidic acid resistance (fusB), resistance to macrolides and lincosamides (ermCandermA), Panton-Valentine leukocidin (PVL) (lukS/lukF-PV), exfoliative toxins (etaandetb), and fibronectin binding protein A (fnbA) were investigated by PCRs in 102 selected preserved strains. Genotyping was performed by SCCmecandagrtyping, whereas clonality was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). A total of 437 cases among 2,137 staphylococcal infections were recorded in 2013 to 2016; they were all SSTIs with the exception of 1 case of primary bacteremia. Impetigo was the predominant clinical entity (371 cases [84.9%]), followed by staphylococcal scalded skin syndrome (21 cases [4.8%]), and there were no abscesses. The number of infections detected annually increased during the study years. All except 3 isolates were methicillin susceptible. The rates of HLR to mupirocin and constitutive resistance to clindamycin were 99% and 20.1%, respectively. Among the 102 tested strains, 100 (98%) weremupApositive and 97 (95%) werefusBpositive, 26/27 clindamycin-resistant strains (96.3%) wereermApositive, 83 strains (81.4%) werelukS/lukFpositive, 95 (93%) carried bothetaandetbgenes, and 99 (97%) werefnbApositive. Genotyping of methicillin-sensitiveS. aureus(MSSA) strains revealed that 96/99 (96.7%) belonged to one main pulsotype, pulsotype 1, classified as sequence type 121 (ST121). The emergence of a single MSSA clone (ST121) causing impetigo was documented. Resistance to topical antimicrobials and a rich toxinogenic profile confer to this clone adaptability for spread in the community.

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