Vancomycin modifies the expression of the agr system in multidrug-resistant Staphylococcus aureus clinical isolates

Published on May 5, 2015in Frontiers in Microbiology4.235
· DOI :10.3389/FMICB.2015.00369
Vicenta Cázares-Domínguez6
Estimated H-index: 6
Sara A. Ochoa10
Estimated H-index: 10
+ 6 AuthorsJuan Xicohtencatl-Cortes19
Estimated H-index: 19
Staphylococcus aureus is an opportunistic pathogen that colonizes human hosts and causes a wide variety of diseases. Two interacting regulatory systems called agr (accessory gene regulator) and sar (staphylococcal accessory regulator) are involved in the regulation of virulence factors. The aim of this study was to evaluate the effect of vancomycin on hld and spa gene expression during the exponential and post-exponential growth phases in multidrug resistant (MDR) S. aureus. Methods. Antibiotic susceptibility was evaluated by the standard microdilution method. The phylogenetic profile was obtained by pulsed-field gel electrophoresis. Polymorphisms of agr and SCCmec were analyzed by multiplex polymerase chain reaction. The expression levels of hld and spa were analyzed by reverse transcription-PCR. An enzyme-linked immunosorbent assay assay was performed to detect protein A, and biofilm formation was analyzed via crystal violet staining. Results. In total, 60.60% (20/33) of S. aureus clinical isolates were MDR. Half (10/20) of the MDR S. aureus isolates were distributed in subcluster 10, with > 90% similarity among them. In the isolates of this subcluster, a high prevalence (100%) for the agrII and the cassette SCCmec II polymorphisms was found. Our data showed significant increases in hld expression during the post-exponential phase in the presence and absence of vancomycin. Significant increases in spa expression, protein A production and biofilm formation were observed during the post-exponential phase when the MDR S. aureus isolates were challenged with vancomycin. Conclusion. The polymorphism agrII, which is associated with nosocomial isolates, was the most prevalent polymorphism in MDR S. aureus. Additionally, under our study conditions, vancomycin modified hld and spa expression in these clinical isolates. Therefore, vancomycin may regulate alternative systems that jointly participate in the regulation of these virulence factors.
📖 Papers frequently viewed together
4 Citations
20193.59BMC Genomics
3 Authors (Kifaya Azmi, ..., Ziad Abdeen)
15 Citations
84 Citations
Methicillin-resistant Staphylococcus aureus (MRSA) is an important opportunistic pathogen that causes both healthcare- and community-acquired infections. An increase in the incidence of these infections may lead to a substantial change in the rate of vancomycin usage. Incidence of reduced susceptibility to vancomycin has been increasing worldwide for the last few years, conferring different levels of resistance to vancomycin as well as producing changes in the cell wall structure. The aim of the...
23 CitationsSource
#1Valéria Cataneli Pereira (UNESP: Sao Paulo State University)H-Index: 11
#2Danilo Flávio Moraes Riboli (UNESP: Sao Paulo State University)H-Index: 8
Last. Maria de Lourdes Ribeiro de Souza da Cunha (UNESP: Sao Paulo State University)H-Index: 19
view all 3 authors...
Background: Methicillin-resistant Staphylococcus aureus (MRSA) are important pathogens in neonatal and pediatric intensive care units, which can cause severe infections in hospitalized children. Detection of the mecA gene and classification of the staphylococcal cassette chromosome mec (SCCmec) permit the characterization of MRSA strains isolated from infections caused by these microorganisms. In contrast, pulsed-field gel electrophoresis (PFGE) is used to type MRSA clones. This method is common...
13 CitationsSource
#1Madeleine G. Sowash (Columbia University)H-Index: 5
#2Anne-Catrin Uhlemann (Columbia University)H-Index: 46
Over the past decade, the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has changed the landscape of S. aureus infections around the globe. Initially recognized for its ability to cause disease in young and healthy individuals without healthcare exposures as well as for its distinct genotype and phenotype, this original description no longer fully encompasses the diversity of CA-MRSA as it continues to expand its niche. Using four case studies, we highli...
34 CitationsSource
#1Marie Pierre Otto (University of Lyon)H-Index: 1
#2Emilie Martin (French Institute of Health and Medical Research)H-Index: 2
Last. Oana Dumitrescu (French Institute of Health and Medical Research)H-Index: 23
view all 9 authors...
Results: For all strains tested, clindamycin and linezolid dramatically reduced mRNA levels of PVL and SpA. Tigecycline also decreased the PVL and SpA mRNA levels of 3/5 and 4/5 strains tested, respectively, whereas daptomycin and vancomycin had no significant effect. PVL and SpA quantification confirmed the concentration-dependent inhibition of PVL and SpA production by clindamycin and, to a lesser extent, by linezolid and tigecycline. Only clindamycin decreased Hla mRNA expression, whereas lin...
59 CitationsSource
#1Rashid RamazanzadehH-Index: 13
#2S. ZamaniH-Index: 1
Last. Saman Zamani (Kurdistan University of Medical Sciences)H-Index: 1
view all 3 authors...
Background and Objectives: The Escherichia coli strains are greatly important in nosocomial and community acquired infections. The aim of this study was to determine the transmission of bacterial infections using genetic analysis. Materials and Methods: Two hundred and thirty Escherichia coli strains, isolated from different clinical samples, were characterized by enterobacterial repetitive intergenic consensus (ERIC)–PCR technique. The results and the similarity between the strains were determi...
21 Citations
#1Tatsuo Yamamoto (Niigata University)H-Index: 26
#2Wei-Chun Hung (Niigata University)H-Index: 7
Last. Akihito Nishiyama (Niigata University)H-Index: 16
view all 4 authors...
Abstract Methicillin-resistant Staphylococcus aureus (MRSA) emerged in 1961, just after the introduction of methicillin as a countermeasure against penicillinase-producing “multidrug-resistant” S. aureus , a threat at that time. Since then, MRSA has posed a continuous threat to medical care as a major multidrug-resistant pathogen in hospitals. In 1997–1999, severe invasive infection with MRSA occurred in the community, and this attracted attention as community-associated MRSA (CA-MRSA). The evol...
24 CitationsSource
#1Stacey L. Kolar (USF: University of South Florida)H-Index: 4
#2J. Antonio Ibarra (Roy J. and Lucille A. Carver College of Medicine)H-Index: 16
Last. Lindsey N. Shaw (USF: University of South Florida)H-Index: 29
view all 8 authors...
Staphylococcus aureus is a highly virulent and successful pathogen that causes a diverse array of diseases. Recently, an increase of severe infections in healthy subjects has been observed, caused by community-associated methicillin-resistant S. aureus (CA-MRSA). The reason for enhanced CA-MRSA virulence is unclear; however, work suggests that it results from hypersecretion of agr-regulated toxins, including secreted proteases. In this study, we explore the contribution of exo-proteases to CA-MR...
110 CitationsSource
#1Meghan F. Davis (Johns Hopkins University)H-Index: 21
#2Amy E. Peterson (Johns Hopkins University)H-Index: 4
Last. Ellen K. Silbergeld (Johns Hopkins University)H-Index: 84
view all 8 authors...
Antimicrobial resistance, particularly in pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), limits treatment options and increases healthcare costs. To understand patient risk factors, including household and animal contact, potentially associated with colonization with multidrug-resistant MRSA isolates, we performed a prospective study of case patients colonized with MRSA on admission to a rural tertiary care hospital. Patients were interviewed and antimicrobial resistance p...
16 CitationsSource
#1Viviana Cafiso (University of Catania)H-Index: 18
#2Taschia Bertuccio (University of Catania)H-Index: 10
Last. Stefania Stefani (University of Catania)H-Index: 48
view all 8 authors...
Glycopeptides are still the gold standard to treat MRSA (Methicillin Resistant Staphylococcus aureus) infections, but their widespread use has led to vancomycin-reduced susceptibility [heterogeneous Vancomycin-Intermediate-Staphylococcus aureus (hVISA) and Vancomycin-Intermediate-Staphylococcus aureus (VISA)], in which different genetic loci (regulatory, autolytic, cell-wall turnover and cell-envelope positive charge genes) are involved. In addition, reduced susceptibility to vancomycin can infl...
64 CitationsSource
#1Hong-Yi Chen (CGU: Chang Gung University)H-Index: 2
#2Chien-Cheng Chen (NKNU: National Kaohsiung Normal University)H-Index: 13
Last. Jwu-Ching Shu (CGU: Chang Gung University)H-Index: 9
view all 6 authors...
The alternative transcription factor σB is responsible for transcription in Staphylococcus aureus during the stress response. Many virulence-associated genes are directly or indirectly regulated by σB. We hypothesized that treatment with antibiotics may act as an environmental stressor that induces σB activity in antibiotic-resistant strains. Several antibiotics with distinct modes of action, including ampicillin (12 µg/ml), vancomycin (16 or 32 µg/ml), chloramphenicol (15 µg/ml), ciprofloxacin ...
29 CitationsSource
Cited By10
Objective The purpose of this study is to assess the in vitro/vivo activities of linezolid plus fosfomycin against Staphylococcus aureus (S. aureus) isolates with varying susceptibility to the study drugs. Methods The increasing concentration stepwise method was used to induce S. aureus resistant strains. The in vitro antibacterial activity of linezolid combined with fosfomycin against S. aureus in vitro was studied by time-kill curve and PAE. The transmission electron microscopy (TEM) was emplo...
Methicillin-resistant Staphylococcus aureus (MRSA) is considered an opportunistic pathogen in humans and is mainly associated with healthcare-associated infections (HCAIs). This bacterium colonizes the skin and mucous membranes of healthy people and causes frequent hospital outbreaks. The aim of this study was to perform molecular typing of the staphylococcal cassette chromosome mec (SCCmec) and agr loci as wells as to establish the pulsotypes and clonal complexes (CCs) for MRSA and methicillin-...
1 CitationsSource
#1Negar Narimisa (IUMS: Iran University of Medical Sciences)H-Index: 2
#2Fatemeh Amraei (IUMS: Iran University of Medical Sciences)H-Index: 2
Last. Faramarz Masjedian Jazi (IUMS: Iran University of Medical Sciences)H-Index: 5
view all 5 authors...
Abstract Objectives Sub-inhibitory concentrations (sub-MICs) of antibiotics reflect the conditions bacteria encounter in tissues and the natural environment. Sub-MICs of antibiotics can induce stress and alter the expression of different bacterial genes. Bacteria react to stress conditions using different mechanisms one of which is Toxin-Antitoxin (TA) systems. This study investigated the expression of TA system genes under oxidative and antibiotic stresses in Klebsiella pneumoniae. Methods To d...
9 CitationsSource
#1Han Yang (SJTU: Shanghai Jiao Tong University)H-Index: 3
#2Su Xu (Fudan University)H-Index: 5
Last. Qingzhong Liu (SJTU: Shanghai Jiao Tong University)H-Index: 10
view all 11 authors...
Antibiotics have been described to modulate bacterial virulence gene expression. This study aimed to assess the changes caused by anti-Staphylococcus agents in the transcription of leucocidin ED (lukED) gene of Staphylococcus aureus strain Newman in vitro and in vivo and to determine whether the altered expression is agr dependent. The bacteria were exposed to subinhibitory concentrations [1/2, 1/4, or 1/8 minimal inhibitory concentration (MIC)] of 11 antibiotics, and the expression of lukE and ...
4 CitationsSource
#1Chunlei Li (Qilu University of Technology)H-Index: 2
#2Chengguang Zhu (Sichuan University)H-Index: 1
Last. Lixin Zhang (ECUST: East China University of Science and Technology)
view all 12 authors...
Abstract The rapid increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections and the cross-resistance of MRSA to other antibiotics create an urgent demand for new therapeutic agents. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, novel peptides were designed based on antimicrobial peptide fragments derived from Aristicluthys nobilia interferon-I to promote anti-MRSA activity and decrease adverse effects. Design ...
10 CitationsSource
#1Nagendran Tharmalingam (Brown University)H-Index: 11
#2Rajamohammed Khader (Brown University)H-Index: 2
Last. Eleftherios Mylonakis (Brown University)H-Index: 2
view all 4 authors...
Antimicrobial drug discovery against drug-resistant bacteria is an urgent need. Beyond agents with direct antibacterial activity, anti-virulent molecules may also be viable compounds to defend against bacterial pathogenesis. Using a high throughput screen (HTS) that utilized, Caenorhabditis elegans infected with methicillin-resistant Staphylococcus aureus (MRSA) strain of MW2, we identified 4-(1,3-dimethyl-2,3-dihydro-1H-benzimidazol-2-yl)phenol (BIP). Interestingly, BIP had no in vitro inhibiti...
5 CitationsSource
#1Qian Yang (Agricultural University of Hebei)H-Index: 35
#1Qian YangH-Index: 1
Last. Shuaihua Zhang (Agricultural University of Hebei)H-Index: 2
view all 7 authors...
Staphylococcus aureus (S. aureus) is an important food-borne pathogen which poses a severe threat to public health worldwide. Rapid detection of S. aureus with high sensitivity is of particular importance for food safety. In this study, a novel single primer isothermal amplification (SPIA) method was established to detect S. aureus in food, targeting the accessory gene regulator (agr) gene with a DNA/RNA primer. The developed SPIA method has the advantages of visualization and avoiding tedious e...
5 CitationsSource
#1Maria MaganaH-Index: 6
#2Christina SeretiH-Index: 2
Last. George P. TegosH-Index: 48
view all 10 authors...
SUMMARY Bacteria can form single- and multispecies biofilms exhibiting diverse features based upon the microbial composition of their community and microenvironment. The study of bacterial biofilm development has received great interest in the past 20 years and is motivated by the elegant complexity characteristic of these multicellular communities and their role in infectious diseases. Biofilms can thrive on virtually any surface and can be beneficial or detrimental based upon the community9s i...
71 CitationsSource
#1Avanish K. VarshneyH-Index: 15
Last. Sushma ShivaswamyH-Index: 1
view all 13 authors...
Staphylococcus aureus can cause devastating and life-threatening infections. With the increase in multidrug resistant strains, novel therapies are needed. Limited success with active and passive immunization strategies have been attributed to S. aureus immune evasion. Here, we report on a monoclonal antibody, 514G3, that circumvents a key S. aureus evasion mechanism by targeting the cell wall moiety Protein A (SpA). SpA tightly binds most subclasses of immunoglobulins via their Fc region, neutra...
29 CitationsSource
#1Elisabeth Hodille (French Institute of Health and Medical Research)H-Index: 8
#2Warren E. Rose (UW: University of Wisconsin-Madison)H-Index: 32
Last. Oana Dumitrescu (French Institute of Health and Medical Research)H-Index: 23
view all 6 authors...
SUMMARY Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host9s immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was...
57 CitationsSource