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Antigens from the methicillin-resistant Staphylococcus aureus (MRSA) cell wall have been shown to be immunogenic in vivo and upregulated during biofilm growth. In this study, we created
purified, recombinant forms of selected antigens and biofilm-upregulated, cell wall-associated proteins. These proteins were
shown to cause a robust polyclonal immu...
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... Research suggests that EbpS binds to elastin peptides and elastin, acting as an adhesin that binds to host cell elastin [16]. As the biofilm matures, microcolonies exhibit different growth characteristics and protein expression depending on their location in the biofilm [17]. Ultimately, biofilms disperse, break down, spread, and repeat the process elsewhere. ...
Background
Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections.
Results
Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of adhesion ability. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST188, ST7, and ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE genes were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cephalothin (94.8%), clindamycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (90.9%), and linezolid (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types.
Conclusions
MRSA strains with biofilm production capability warrant increased vigilance.
... MRSA strains can generate biofilm as a growth and survivability mechanism in addition to their resistance to antibiotics. This capacity is facilitated by the strains' strong compliance, increased drug resistance, and decreased sanitiser efficiency (Brady et al. 2007;Craft et al. 2019). Coagulase negativity With a few rare exceptions, S. aureus (CoNS) and S. aureus were both susceptible to glycopeptides. ...
Staphylococcus aureus is one of the most ubiquitous organisms found all across the globe. They usually colonize the nasal cavity or outer surface of the human body, behaving as a commensal or pathogen according to the conditions. In the past, they were easily fended off by using regularly available antibiotics. This misuse of antibiotics against S. aureus soon led to the development of antibiotic resistance in the bacteria. At first, it became resistant to the methicillin group of antibiotics. An alarm was raised among physicians due to the lost effect of methicillin antibiotics and they soon switched to vancomycin. Vancomycin proved effective even in the case of methicillin-resistant bacteria. However, this remedy soon met its end as vancomycin-resistant isolates of S. aureus were discovered later on. Although most of the isolates were from animal sources, it still threatened global public health due to the phenomenon of zoonosis leading to the transfer of vancomycin-resistant Staphylococcus aureus (VRSA) to the human population. This is a matter of grave concern for the health security of the human population as zoonosis can lead to further aggregation of already rising antibiotic resistance reducing the overall effect of antibiotics. This will in turn produce diseases that will be incurable with the current antibiotics we have available. A forecast of such incurable maladies suggests that humanity will be once again facing the same era of health problems as it faced in medieval times. Commonly curable diseases will become fatal for mankind and life expectancy will begin to reduce considerably. This will halt the progress of humanity pushing us back hundreds of years. Such issues require the implementation of strict rules regarding the prescription and use of antibiotics. Furthermore, stringent regulations should be implemented to prevent the spread of infectious diseases. Reduction in disease prevalence will ultimately lead to less use of antibiotics and hence lower chances of resistance development in bacteria.
... Masaki also demonstrated [31] comparable results to our study, who isolated 19 clinical MRSA strains from the clinical floor. In an alternate study, Brady isolated 25 MRSA strains from hospital cots, showing the existence of this microbe on distinctive locations [32]. Another study was conducted which reported that health care experts again contaminate their hands throughout interferences of patient treatment by touching things, for example, a computer mouse, caution catches and pens before administering the patients [33]. ...
Background: Nosocomial infections present a major threat because of the increased prevalence of clinical
cases appearing among both developed as well as developing countries thus resulting in an alarming
condition. This descriptive study was designed to determine the prevalence of hospital acquired
vancomycin resistant Staphylococcus aureus (VRSA) in intensive care units (ICU) of different hospitals of Lahore.
Methods: Sixty three swab samples were collected from different local hospitals in Lahore. The study was
conducted at the Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore from
2013 to 2014. Methicillin sensitive Staphylococcus aureus (MSSA), Methicillin resistant Staphylococcus aureus
(MRSA) and VRSA were isolated and confirmed using Clinical & Laboratory Standard Institute (CLSI), 2015
guidelines. vanA gene was amplified to determine the molecular basis of resistance of all VRSA isolates by using
strain of S. aureus (ATCC 29213) as a gold standard.
Results: Prevalence of VRSA is comparatively low in the hospital settings of Lahore than MRSA. Out of sixty
three S. aureus, four (6%) isolates were VRSA positive, and eight isolates (17%) showed intermediate resistance.
The absence of vanA gene in VRSA showed that mechanism of resistance is other than vanA gene transfer.
Conclusions: Presence of VRSA in hospital settings is alarming for health care workers, patients and
researchers and it also highlights the importance of alternative medicines to cure infections.
... Some MSCRAMMS, such as SdrC and FnBPs, can self-associate to serve this role [14,16], but IgG binding protein A (Spa) is the dominant component of the extracellular matrix that facilitates bacterial aggregation [17]. As a biofilm matures, microcolony clusters begin to exhibit different growth characteristics and protein expression depending on their location within the biofilm [18]. Eventually, the biofilm disperses or is disrupted, shedding these clusters to spread and repeat the process elsewhere. ...
A key characteristic of Staphylococcus aureus infections, and one that also varies phenotypically between clones, is that of biofilm formation, which aids in bacterial persistence through increased adherence and immune evasion. Though there is a general understanding of the process of biofilm formation - adhesion, proliferation, maturation and dispersal - the tightly orchestrated molecular events behind each stage, and what drives variation between S. aureus strains, has yet to be unravelled. Herein we measure biofilm progression and dispersal in real-time across the five major S. aureus CDC-types (USA100-USA500) revealing adherence patterns that differ markedly amongst strains. To gain insight into this, we performed transcriptomic profiling on these isolates at multiple timepoints, compared to planktonically growing counterparts. Our findings support a model in which eDNA release, followed by increased positive surface charge, perhaps drives initial abiotic attachment. This is seemingly followed by cooperative repression of autolysis and activation of poly-N-acetylglucosamine (PNAG) production, which may indicate a developmental shift in structuring the biofilm matrix. As biofilms mature, diminished translational capacity was apparent, with 53 % of all ribosomal proteins downregulated, followed by upregulation of anaerobic respiration enzymes. These findings are noteworthy because reduced cellular activity and an altered metabolic state have been previously shown to contribute to higher antibiotic tolerance and bacterial persistence. In sum, this work is, to our knowledge, the first study to investigate transcriptional regulation during the early, establishing phase of biofilm formation, and to compare global transcriptional regulation both temporally and across multiple clonal lineages.
... We previously characterized and described MRSA biofilm-specific proteins that were immunogenic in the rabbit model of osteomyelitis and upregulated in the biofilm mode of growth in vitro (30). To develop a biofilm-specific assay, recombinant proteins for select S. aureus in vivo-expressed proteins (SACOL0486, glucosaminidase, or SACOL0688) were produced and purified as described previously (31,37). ...
Prosthetic joint infections are difficult to diagnose and treat due to biofilm formation by the causative pathogens. Pathogen identification relies on microbial culture that requires days-to-weeks, and in the case of chronic biofilm infections, lacks sensitivity. Diagnosis of infection is often delayed past the point of effective treatment such that only the removal of the implant is curative. Early diagnosis of an infection based on antibody detection might lead to less invasive, early interventions. Our study examined antibody-based assays against the Staphylococcus aureus biofilm-upregulated antigens SAOCOL0486 (a lipoprotein), glucosaminidase (a domain of SACOL1062), and SACOL0688 (the manganese transporter MntC) for detection of chronic S. aureus infection. We evaluated these antigens by enzyme-linked immunosorbent assay (ELISA) using sera from naive rabbits and rabbits with S. aureus- mediated osteomyelitis, and then validated a proof of concept for the lateral flow assay (LFA). The SACOL0688 LFA demonstrated 100% specificity and 100% sensitivity. We demonstrated the clinical diagnostic utility of the SACOL0688 antigen using synovial fluid (SF) from humans with orthopedic implant infections. Elevated antibody levels to SACOL0688 in clinical SF specimens correlated to 91% sensitivity and 100% specificity for the diagnosis of S. aureus infection by ELISA. We found measuring antibodies levels to SACOL0688 in SF using ELISA or LFA provides a tool for the sensitive and specific diagnosis of S. aureus prosthetic joint infection. Development of the LFA diagnostic modality is a desirable, cost-effective option, potentially providing rapid readout in minutes for chronic biofilm infections.
... Cephalosporin antibiotics are even more resistant to β-lactamases, although some β-lactamases have an increased affinity for cephalosporins (Issa, 2019), Results showed that the most effective antagonists against isolated clinical MRSA isolates Wounds and burns were Ciprofloxacin and Vancomycin This is consistent with result (Shekarabi et al., 2017), The lack of resistance to Vancomycin is due to its lack of vanA and vanB gene (Zhang et al., 2004), indicated that resistance to S. aureus clinical isolates was 43% for Gentamicin contrasting study while 13% for Chloramphenicol which is similar to the current study (Bush et al.,1995). our results are compatible with those obtained by Researcher (Brady et al., 2007) as they observed that all isolates were resistant to Oxacilline and Methicillin and other β-lactam antibiotics, While Al-Hossainy (2007), showed that VRSA were 20% among S. aureus, the result is close to our results, This results disagreed with finding of Al-Geobory (2011) in that the rate of resistant to vancomycin was 2.27%. Where the VRSA isolate among S. aureus is isolates 4 out of 50 (8%) (Mohammed, 2011). ...
... Cephalosporin antibiotics are even more resistant to β-lactamases, although some β-lactamases have an increased affinity for cephalosporins (Issa, 2019), Results showed that the most effective antagonists against isolated clinical MRSA isolates Wounds and burns were Ciprofloxacin and Vancomycin This is consistent with result (Shekarabi et al., 2017), The lack of resistance to Vancomycin is due to its lack of vanA and vanB gene (Zhang et al., 2004), indicated that resistance to S. aureus clinical isolates was 43% for Gentamicin contrasting study while 13% for Chloramphenicol which is similar to the current study (Bush et al.,1995). our results are compatible with those obtained by Researcher (Brady et al., 2007) as they observed that all isolates were resistant to Oxacilline and Methicillin and other β-lactam antibiotics, While Al-Hossainy (2007), showed that VRSA were 20% among S. aureus, the result is close to our results, This results disagreed with finding of Al-Geobory (2011) in that the rate of resistant to vancomycin was 2.27%. Where the VRSA isolate among S. aureus is isolates 4 out of 50 (8%) (Mohammed, 2011). ...
Panton-Valentine leukocidin (luk-pv) producing Methicillin Resistant Staphylococcus aureus (MRSA) is a serious health threating pathogen causes a skin and soft tissue infections. Accurate and rapid diagnosis of this pathogen determination the antibiotics resistance and virulence patterns is contributed significantly in effective treatment and improves the proceedings of infection control. In this study, single reaction of polymerase chain reaction technique applied to characterize the MRSA pathogen and determine the prevalence of its most important virulence genes including; luk-pv, mecA and nuc genes encoded for Panton-Valentine leukocidin, penicillin binding protein and thermo stable nuclease respectively, in addition to species-specific detection using 16S rRNA. Successful reactions were gathered in one multiplex reaction. In total 155 of different clinical samples were collected from main hospitals in Baghdad. The results showed variant profile of resistance against 18 antibiotics; complete resistance (100%) toward Methicillin and Oxacilline. High resistance to Ceftazidime (92.85%), Ampicillin (91%), Piperacillin (85.7%) and penicillin G (77%). Moderate resistance was to Tetracycline (67%), Cefotaxime (58.57%) and Clindamycin (34.28%). While low resistance was towards Tobramycin (14.28%), Vancomycin (17%), Gentamicin (18.57%), Levofloxacin (11.4%), Ciprofloxacin (4%), Chloramphenicol (9%), Erythromycin (14%), Rifampin (15.7%) and Amikacin (25.7%). Molecular screening using PCR technique showed 100%-228 bp, 91%-433bp, 100%-147bp and 85.7%-270bp towards 16SrRNA, luk-pv, mecA and nuc genes respectively. No clear correlation was observed between existence of pvl nuc and antibiotic pattern. Obviously, the luk-pv prevalence is significantly high in Baghdad. Optimization the monoplex PCR reactions in union multiplex reaction is succeed. Therefore, such sensitive and specific with no false positive result is reliable assay can be adapts for routine use in a diagnosis of MRSA pathogen.
... S. aureus biofilms exhibit different protein expression profiles compared to their planktonic counterparts (19)(20)(21). Although the bacterial biofilm is recalcitrant to clearance by the host immune response, proteins restricted to the biofilm growth phenotype are recognized by the immune system and elicit a humoral response (22). In an effort to target and eradicate S. aureus throughout all stages of biofilm maturation, Brady et al. created a vaccine that boosts and directs the humoral response against biofilm-specific antigens that have sustained expression throughout infection. ...
... The disparity between the elevated IgG levels and the limited clearance potential of the anti-SACOL0688 antibodies may be the direct consequence of heterogeneity within the biofilm. Indeed, confocal microscopy of in vitro S. aureus biofilms using anti-SACOL0688 antibodies found that SACOL0688 expression was restricted to distinct pockets of microcolonies within the biofilm (22). These data support the importance of the multivalent vaccine approach to enhance coverage of the biofilm. ...
... Studies were performed with methicillin-resistant S. aureus (MRSA) clinical isolate, MRSA-M2, that was obtained from the University of Texas Medical Branch (Galveston, TX). The MRSA-M2 isolate has been used for immunoproteomic and transcriptomic analyses (20,22,23,25,31,32,(36)(37)(38)(39)(40)(41)(42)(43), and the draft genome was deposited in GenBank under accession number AMTC00000000 (36). The strain was maintained on Trypticase soy agar (TSA) with 5% blood (Becton, Dickinson and Company, Franklin Lakes, NJ) and 0.03 mg/ml oxacillin and grown in tryptic soy broth (TSB) (Sigma-Aldrich, St. Louis, MO) to generate the bacterial inocula. ...
Staphylococcus aureus is a causative agent of chronic biofilm-associated infections that are recalcitrant to resolution by the immune system or antibiotics. To combat these infections, an anti-staphylococcal, biofilm-specific quadrivalent vaccine against an osteomyelitis model in rabbits has previously been developed and shown to be effective at eliminating biofilm-embedded bacterial populations. However, the addition of antibiotics was required to eradicate remaining planktonic populations. In this study a planktonic up-regulated antigen was combined with the quadrivalent vaccine to remove the need for antibiotic therapy. Immunization with this pentavalent vaccine followed by intraperitoneal challenge of BALB/c mice with S. aureus resulted in 16.7% versus 91.7% mortality in pentavalent vaccine and control groups, respectively (p<0.001). Complete bacterial elimination was found in 66.7% of the pentavalent cohort, while only 8.3% of the control animals cleared the infection (p<0.05). Further protective efficacy was observed in immunized rabbits following intramedullary challenge with S. aureus, where 62.5% of the pentavalent cohort completely cleared the infection versus none of the control animals (p<0.05). Passive immunization of BALB/c mice with serum IgG against the vaccine antigens prior to intraperitoneal challenge with S. aureus prevented mortality in 100% of mice and eliminated bacteria in 33.3% of the challenged mice. These results demonstrate that targeting both the planktonic and biofilm stages with the pentavalent vaccine or the IgG elicited by immunization can effectively protect against S. aureus infection.
... When difference occurs in concentration of nutrients, oxygen and acceptor of electron, gene expression affected to be heterogeneous into biofilm. It also can be even different in cells neighboring to biofilm (Brady et al., 2007). In response to these environmental signals, sigma factor proteins and small non-coding RNAs (sRNAs) transmit regulatory signals to various genes to help the bacteria for adapt (Ghaz-Jahanian et al., 2013). ...
Silver nanoparticles was considered a powerful antimicrobial agents recently especially after increasing incidence of diseases associated with biofilm and multi-drug resistant pathogens which necessary required to find a novel path to eradicate that’s challenge. So the aim of present study was to synthesize silver nanoparticles by biological method using bacteria (Enterobacter cloacae) to eradicate biofilm forming bacteria as phenotypic and genotypic levels and comparison with chemical synthesis of nanoparticles.
The study was carried out at the period of February/ 2017 to January/ 2018. Urine samples 65 were collected from catheterized inpatients who admitted to Al Diwaniya Teaching, Al Hilla Teaching, Al Qasim and Al Hashimiya Hospitals. The results showed that 58 (89.2%) gave positive growth, 28 (43%) as biofilm producer after phenotypically biofilm detection assay with congo red and tissue culture plate methods and genetically using polymerase chain reaction (PCR) for detecting iacA, smaI and esaL genes encoding biofilm for three bacterial isolates (Staphylococcus lentus, Serratia fonticola and Pantoea sp.) were the results established that all tested bacteria had own biofilm genes. All biofilm bacterial isolates were diagnosed and identified by VITEK2 system.
... Zróżnicowanie ekspresji genów w biofilmie wykazali również Brady i wsp. [6], na przykładzie białek związanych ze ścianą komórkową. Jednym z nich była glukozaminidaza, białko zaangażowane w hydrolizę peptydoglikanu, która zachodzi z dużą wydajnością w komórkach aktywnie dzielących się. ...
The ability to form biofilm is an important virulence factor of many microorganisms. Infections involving biofilms account for approx. 65% of all human infections. Biofilms may develop on intravascular catheters or implanted devices such as prosthetic heart valves. Implanted devices are covered by biofilm and become reservoirs of microorganisms which can be a cause of persistent infections (endocarditis, deep tissue abscesses, septic arthritis, and osteomyelitis). Treatment of infections caused by biofilm-growing cells is linked to a high risk of failure due to an extreme resistance to antimicrobial agents and increased capacity to evade the immune responses. A large number of biofilm-associated infections involve Staphylococcus aureus. Treatment of staphylococcal infections is a great challenge for clinicians because of the presence of various mechanisms of resistance to antibiotics in S. aureus, for example methicillin resistance and biofilm production. Therapeutic difficulties related with antibiotic-resistant bacteria and limitations in research on new antimicrobials were the reasons that nearly 100 years after
discovery, bacteriophages caught the attention of scientists around the world as a new therapeutic
option for bacterial infections. Numerous in vitro studies on S. aureus strains showed
that phages can both prevent biofilm formation and contribute to the elimination of bacteria
from the mature biofilm structure. The major role in biofilm eradication play depolymerases
produced by some phages which facilitate their penetration into the inner layers of biofilm
by disturbing the biofilm structure. This leads to the conclusion that bacteriophages treatment
might become a new strategy in the prevention and eradication of infectious bacterial
biofilms, including these formed by S. aureus.
