scholarly journals Phylogenomic Analysis Reveals the Evolutionary Route of Resistant Genes in Staphylococcus aureus

2019 ◽  
Vol 11 (10) ◽  
pp. 2917-2926 ◽  
Author(s):  
Jiffy John ◽  
Sinumol George ◽  
Sai Ravi Chandra Nori ◽  
Shijulal Nelson-Sathi

Abstract Multidrug-resistant Staphylococcus aureus is a leading concern worldwide. Coagulase-Negative Staphylococci are claimed to be the reservoir and source of important resistant elements in S. aureus. However, the origin and evolutionary route of resistant genes in S. aureus are still remaining unknown. Here, we performed a detailed phylogenomic analysis of 152 completely sequenced S. aureus strains in comparison with 7,529 non-Staphylococcus aureus reference bacterial genomes. Our results reveal that S. aureus has a large open pan-genome where 97 (55%) of its known resistant-related genes belonging to its accessory genome. Among these genes, 47 (27%) were located within the Staphylococcal Cassette Chromosome mec (SCCmec), a transposable element responsible for resistance against major classes of antibiotics including beta-lactams, macrolides, and aminoglycosides. However, the physically linked mec-box genes (MecA–MecR–MecI) that are responsible for the maintenance of SCCmec elements is not unique to S. aureus, instead it is widely distributed within Staphylococcaceae family. The phyletic patterns of SCCmec-encoded resistant genes in Staphylococcus species are significantly different from that of its core genes indicating frequent exchange of these genes between Staphylococcus species. Our in-depth analysis of SCCmec-resistant gene phylogenies reveals that genes such as blaZ, ble, kmA, and tetK that are responsible for beta-lactam, bleomycin, kanamycin, and tetracycline resistance in S. aureus were laterally transferred from non-Staphylococcus sources. In addition, at least 11 non-SCCmec-encoded resistant genes in S. aureus, were laterally acquired from distantly related species. Our study evidently shows that gene transfers played a crucial role in shaping the evolution of antibiotic resistance in S. aureus.

2019 ◽  
Author(s):  
Jiffy John ◽  
Sinumol George ◽  
Sai Ravi Chandra Nori ◽  
Shijulal Nelson-Sathi

AbstractMulti-drug resistant S. aureus is a leading concern worldwide. Coagulase-Negative Staphylococci (CoNS) are claimed to be the reservoir and source of important resistant elements in S. aureus. However, the origin and evolutionary route of resistant genes in S. aureus are still remaining unknown. Here, we performed a detailed phylogenomic analysis of 152 completely sequenced S. aureus strains in comparison with 7,529 non-S. aureus reference bacterial genomes. Our results reveals that S. aureus has a large open pan-genome where 97 (55%) of its known resistant related genes belonging to its accessory genome. Among these genes, 47 (27%) were located within the Staphylococcal Cassette Chromosome (SCCmec), a transposable element responsible for resistance against major classes of antibiotics including beta-lactams, macrolides and aminoglycosides. However, the physically linked mec-box genes (MecA-MecR-MecI) that are responsible for the maintenance of SCCmec elements is not unique to S. aureus, instead it is widely distributed within Staphylococcaceae family. The phyletic patterns of SCCmec encoded resistant genes in Staphylococcus species are significantly different from that of its core genes indicating frequent exchange of these genes between Staphylococcus species. Our in-depth analysis of SCCmec resistant gene phylogenies reveals that genes such as blaZ, ble, kmA and tetK that are responsible for beta-lactam, bleomycin, kanamycin and tetracycline resistance in S. aureus were laterally transferred from non-Staphylococcus sources. In addition, at least 11 non-SCCmec encoded resistant genes in S. aureus, mostly present in plasmid are laterally acquired from distantly related species. Our study evidently shows that gene transfers played a crucial role in shaping the evolution of antibiotic resistance in S. aureus.


2015 ◽  
Vol 59 (5) ◽  
pp. 2583-2587 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Nachum Kaplan ◽  
Ronald N. Jones ◽  
David J. Farrell

ABSTRACTStaphylococcus aureusand coagulase-negative staphylococci (CoNS) are responsible for a wide variety of human infections. The investigational antibacterial Debio1450 (previously AFN-1720), a prodrug of Debio1452 (previously AFN-1252), specifically targets staphylococci without significant activity against other Gram-positive or Gram-negative species. Debio1452 inhibits FabI, an enzyme critical to fatty acid biosynthesis in staphylococci. The activity of Debio1452 against CoNS, methicillin-susceptibleS. aureus(MSSA), and methicillin-resistantS. aureus(MRSA), including significant clones, was determined. A globally diverse collection of 574 patient isolates from 35 countries was tested that included CoNS (6 species, 103 strains), MSSA (154 strains), MRSA (163 strains), and molecularly characterized strains (includingspa-typed MRSA clones; 154 strains). The isolates were tested for susceptibility by CLSI broth microdilution methods against Debio1452 and 10 comparators. The susceptibility rates for the comparators were determined using CLSI and EUCAST breakpoint criteria. AllS. aureusand CoNS strains were inhibited by Debio1452 concentrations of ≤0.12 and ≤0.5 μg/ml, respectively. The MIC50s for MSSA, MRSA, and molecularly characterized MRSA strains were 0.004 μg/ml, and the MIC90s ranged from 0.008 to 0.03 μg/ml. The MICs were higher for the CoNS isolates (MIC50/90, 0.015/0.12 μg/ml). AmongS. aureusstrains, resistance was common for erythromycin (61.6%), levofloxacin (49.0%), clindamycin (27.6%), tetracycline (15.7%), and trimethoprim-sulfamethoxazole (7.0%). Debio1452 demonstrated potent activity against MSSA, MRSA, and CoNS. Debio1452 showed significantly greater activity overall (MIC50, 0.004 μg/ml) than the other agents tested against these staphylococcal species, which included dominant MRSA clones and strains resistant to currently utilized antimicrobial agents.


2011 ◽  
Vol 140 (8) ◽  
pp. 1366-1371 ◽  
Author(s):  
M. ZHANG ◽  
M. O'DONONGHUE ◽  
M. V. BOOST

SUMMARYEnvironmental staphylococcal contamination was investigated by culture of 400 automated teller machines (ATMs). Isolates were characterized for antibiotic and antiseptic susceptibility, carriage of antiseptic resistance genes (QAC genes), and spa types. MRSA, which was similar to local clinical isolates, was present on two (0·5%) of the 62 (15·5%) ATMs that yielded Staphylococcus aureus. QAC genes were more common in coagulase-negative staphylococci (qacA/B 26·0%, smr 14%) than S. aureus (11·3% qacA/B, 1·6% smr). QAC-positive isolates had significantly higher minimum inhibitory concentrations/minimum bactericidal concentrations to benzalkonium chloride and chlorhexidine digluconate. QAC gene presence was significantly associated with methicillin and tetracycline resistance. Survival of staphylococci, including MRSA, on common access sites may be facilitated by low disinfectant concentrations, which select for disinfectant-tolerant strains, while co-selecting for antibiotic-resistance determinants. Disinfection procedures should be performed correctly to help prevent spread of resistant pathogens from reservoirs in the community.


2008 ◽  
Vol 21 (5) ◽  
pp. 363-370 ◽  
Author(s):  
Jessica A. Starr ◽  
Georgia W. Fox ◽  
Jennifer K. Clayton

Streptococcus pneumoniae represents an important pathogen in numerous community-acquired respiratory infections. Penicillin resistance to Streptococcus pneumoniae in the United States has approached 35%. Additionally, there has been a significant increase in Streptococcus pneumoniae resistance among many other antimicrobial agents such as cephalosporins, macrolides, trimethoprim–sulfamethoxazole, clindamycin, tetracyclines, and chloramphenicol. Several nationwide surveillance programs have been implemented to quantify the prevalence of Streptococcus pneumoniae resistance in the United States. Overall, beta-lactam, macrolide, trimethoprim–sulfamethoxazole, and tetracycline resistance has increased over the past decade while later generation fluoroquinolones (levofloxacin and moxifloxacin) resistance has remained low. Controlling the spread of resistant pneumococcal isolates and preventing the development of both fluoroquinolone and multidrug resistant isolates will require a multidisciplinary approach involving physicians, pharmacists, microbiologists, and epidemiologists.


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
David Patrick Kateete ◽  
Benon B. Asiimwe ◽  
Raymond Mayanja ◽  
Brian Mujuni ◽  
Freddie Bwanga ◽  
...  

Abstract Background Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda. Methods Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health and Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD Phoenix™ system. Genotyping was performed by spa and SCCmec typing. Results The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials –trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [p < 0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [p < 0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [p < 0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [p = 0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [p < 0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected among MRSA, of which t037 and t064 were predominant and associated with SCCmec types I and IV, respectively. Fourteen spa types were detected in MSSA which consisted mainly of t645 and t4353. Conclusions S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.


2019 ◽  
Author(s):  
David Kateete ◽  
Benon B Asiimwe ◽  
Raymond Mayanja ◽  
Brian Mujuni ◽  
Freddie Bwanga ◽  
...  

Abstract Background: Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda. Methods: Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health & Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD PhoenixTM system. Genotyping was performed by spa typing. Results: The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials –trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [P<0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [P<0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [P<0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [P=0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [P<0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected in MRSA, of which t037 & t064 were predominant and associated with SCCmec types I & IV, respectively. Fourteen spa types were detected in MSSA, of which t645 & t4353 were predominant. Conclusions: S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.


PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258592
Author(s):  
Christopher R. Miller ◽  
Jonathan M. Monk ◽  
Richard Szubin ◽  
Andrew D. Berti

Understating how antibiotic tolerance impacts subsequent resistance development in the clinical setting is important to identifying effective therapeutic interventions and prevention measures. This study describes a patient case of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia which rapidly developed resistance to three primary MRSA therapies and identifies genetic and metabolic changes selected in vivo that are associated with rapid resistance evolution. Index blood cultures displayed susceptibility to all (non-beta-lactam) antibiotics with the exception of trimethoprim/ sulfamethoxazole. One month after initial presentation, during the same encounter, blood cultures were again positive for MRSA, now displaying intermediate resistance to vancomycin and ceftaroline and resistance to daptomycin. Two weeks later, blood cultures were positive for a third time, still intermediate resistant to vancomycin and ceftaroline and resistant to daptomycin. Mutations in mprF and vraT were common to all multidrug resistant isolates whereas mutations in tagH, agrB and saeR and secondary mprF mutation emerged sequentially and transiently resulting in distinct in vitro phenotypes. The baseline mutation rate of the patient isolates was unremarkable ruling out the hypermutator phenotype as a contributor to the rapid emergence of resistance. However, the index isolate demonstrated pronounced tolerance to the antibiotic daptomycin, a phenotype that facilitates the subsequent development of resistance during antibiotic exposure. This study exemplifies the capacity of antibiotic-tolerant pathogens to rapidly develop both stable and transient genetic and phenotypic changes, over the course of a single patient encounter.


2019 ◽  
Author(s):  
David Kateete ◽  
Benon B Asiimwe ◽  
Raymond Mayanja ◽  
Brian Mujuni ◽  
Freddie Bwanga ◽  
...  

Abstract Background: Staphylococcus aureus carriage is a known risk factor for staphylococcal disease. However, the carriage rates vary by country, demographic group and profession. This study aimed to determine the S. aureus carriage rate in children in Eastern Uganda, and identify S. aureus lineages that cause infection in Uganda. Methods: Nasopharyngeal samples from 742 healthy children less than 5 years residing in the Iganga/Mayuge Health and Demographic Surveillance Site in Eastern Uganda were processed for isolation of S. aureus. Antibiotic susceptibility testing based on minimum inhibitory concentrations (MICs) was determined by the BD PhoenixTM system. Genotyping was performed by spa and SCCmec typing. Results: The processed samples yielded 144 S. aureus isolates (one per child) therefore, the S. aureus carriage rate in children was 19.4% (144/742). Thirty one percent (45/144) of the isolates were methicillin resistant (MRSA) yielding a carriage rate of 6.1% (45/742). All isolates were susceptible to rifampicin, vancomycin and linezolid. Moreover, all MRSA were susceptible to vancomycin, linezolid and clindamycin. Compared to methicillin susceptible S. aureus (MSSA) isolates (68.8%, 99/144), MRSA isolates were more resistant to non-beta-lactam antimicrobials –trimethoprim/sulfamethoxazole 73.3% (33/45) vs. 27.3% (27/99) [p<0.0001]; erythromycin 75.6% (34/45) vs. 24.2% (24/99) [p<0.0001]; chloramphenicol 60% (27/45) vs. 19.2% (19/99) [p<0.0001]; gentamicin 55.6% (25/45) vs. 25.3% (25/99) [p=0.0004]; and ciprofloxacin 35.6% (16/45) vs. 2% (2/99) [p<0.0001]. Furthermore, 42 MRSA (93.3%) were multidrug resistant (MDR) and one exhibited high-level resistance to mupirocin. Overall, 61 MSSA (61.6%) were MDR, including three mupirocin and clindamycin resistant isolates. Seven spa types were detected among MRSA, of which t037 and t064 were predominant and associated with SCCmec types I and IV, respectively. Fourteen spa types were detected in MSSA which consisted mainly of t645 and t4353. Conclusions: S. aureus carriage rate in healthy children in Eastern Uganda is high and comparable to rates for hospitalized patients in Kampala. The detection of mupirocin resistance is worrying as it could rapidly increase if mupirocin is administered in a low-income setting. S. aureus strains of spa types t064, t037 (MRSA) and t645, t4353 (MSSA) are prevalent and could be responsible for majority of staphylococcal infections in Uganda.


2008 ◽  
Vol 52 (4) ◽  
pp. 1430-1437 ◽  
Author(s):  
George G. Zhanel ◽  
Mel DeCorby ◽  
Nancy Laing ◽  
Barb Weshnoweski ◽  
Ravi Vashisht ◽  
...  

ABSTRACT Between 1 September 2005 and 30 June 2006, 19 medical centers collected 4,180 isolates recovered from clinical specimens from patients in intensive care units (ICUs) in Canada. The 4,180 isolates were collected from 2,292 respiratory specimens (54.8%), 738 blood specimens (17.7%), 581 wound/tissue specimens (13.9%), and 569 urinary specimens (13.6%). The 10 most common organisms isolated from 79.5% of all clinical specimens were methicillin-susceptible Staphylococcus aureus (MSSA) (16.4%), Escherichia coli (12.8%), Pseudomonas aeruginosa (10.0%), Haemophilus influenzae (7.9%), coagulase-negative staphylococci/Staphylococcus epidermidis (6.5%), Enterococcus spp. (6.1%), Streptococcus pneumoniae (5.8%), Klebsiella pneumoniae (5.8%), methicillin-resistant Staphylococcus aureus (MRSA) (4.7%), and Enterobacter cloacae (3.9%). MRSA made up 22.3% (197/884) of all S. aureus isolates (90.9% of MRSA were health care-associated MRSA, and 9.1% were community-associated MRSA), while vancomycin-resistant enterococci (VRE) made up 6.7% (11/255) of all enterococcal isolates (88.2% of VRE had the vanA genotype). Extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae occurred in 3.5% (19/536) and 1.8% (4/224) of isolates, respectively. All 19 ESBL-producing E. coli isolates were PCR positive for CTX-M, with bla CTX-M-15 occurring in 74% (14/19) of isolates. For MRSA, no resistance against daptomycin, linezolid, tigecycline, and vancomycin was observed, while the resistance rates to other agents were as follows: clarithromycin, 89.9%; clindamycin, 76.1%; fluoroquinolones, 90.1 to 91.8%; and trimethoprim-sulfamethoxazole, 11.7%. For E. coli, no resistance to amikacin, meropenem, and tigecycline was observed, while resistance rates to other agents were as follows: cefazolin, 20.1%; cefepime, 0.7%; ceftriaxone, 3.7%; gentamicin, 3.0%; fluoroquinolones, 21.1%; piperacillin-tazobactam, 1.9%; and trimethoprim-sulfamethoxazole, 24.8%. Resistance rates for P. aeruginosa were as follows: amikacin, 2.6%; cefepime, 10.2%; gentamicin, 15.2%; fluoroquinolones, 23.8 to 25.5%; meropenem, 13.6%; and piperacillin-tazobactam, 9.3%. A multidrug-resistant (MDR) phenotype (resistance to three or more of the following drugs: cefepime, piperacillin-tazobactam, meropenem, amikacin or gentamicin, and ciprofloxacin) occurred frequently in P. aeruginosa (12.6%) but uncommonly in E. coli (0.2%), E. cloacae (0.6%), or K. pneumoniae (0%). In conclusion, S. aureus (MSSA and MRSA), E. coli, P. aeruginosa, H. influenzae, Enterococcus spp., S. pneumoniae, and K. pneumoniae are the most common isolates recovered from clinical specimens in Canadian ICUs. A MDR phenotype is common for P. aeruginosa isolates in Canadian ICUs.


Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 136
Author(s):  
Nicholas T. K. D. Dayie ◽  
Mary-Magdalene Osei ◽  
Japheth A. Opintan ◽  
Patience B. Tetteh-Quarcoo ◽  
Fleischer C. N. Kotey ◽  
...  

This cross-sectional study investigated the Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA) nasopharyngeal carriage epidemiology in Accra approximately five years post-pneumococcal conjugate vaccines introduction in the country. Archived nasopharyngeal swabs collected from 410 children aged under five years old were bacteriologically cultured. The resultant S. aureus isolates were subjected to antimicrobial susceptibility testing and screening for carriage of the mecA and LukF-PV (pvl) genes, following standard procedures. The data obtained were analyzed with Statistical Products and Services Solutions (SPSS) using descriptive statistics and Chi square tests of associations. The isolated bacteria decreased across coagulase-negative Staphylococci (47.3%, n = 194), S. aureus (23.2%, n = 95), Diphtheroids (5.4%, n = 22), Micrococcus species (3.7%, n = 15), Klebsiella pneumoniae (3.2%, n = 13), Moraxella species and Citrobacter species (1.5% each, n = 6), Escherichia coli, Enterobacter species, and Pseudomonas species (0.9% each, n = 2). The MRSA carriage prevalence was 0.49% (n = 2). Individuals aged 37–48 months recorded the highest proportion of S. aureus carriage (32.6%, 31/95). Resistance of S. aureus to the antibiotics tested were penicillin G (97.9%, n = 93), amoxiclav (20%, n = 19), tetracycline (18.9%, n = 18), erythromycin (5.3%, n = 5), ciprofloxacin (2.1%, n = 2), gentamicin (1.1%, n = 1), cotrimoxazole, clindamycin, linezolid, and teicoplanin (0% each). No inducible clindamycin resistance was observed for the erythromycin-resistant isolates. Three (3.2%) of the isolates were multidrug resistant, of which 66.7% (2/3) were MRSA. The pvl gene was associated with 59.14% (55/93) of the methicillin-sensitive S. aureus (MSSA) isolates, but was not detected among any of the MRSA isolates.


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