Distribution of edin in Staphylococcus aureus isolated from diabetic foot ulcers

Staphylococcus aureus is both a common colonizer of human skin and the most frequently isolated pathogen in diabetes foot infections (DFIs). The spread of DFI to soft tissue and bony structures is a major causal factor for lower-limb amputation. It is therefore of great importance to differentiate colonizing from infecting strains of S. aureus. Epidermal cell differentiation inhibitors known as EDIN and EDIN-like factors, a group of toxins targeting RhoA master regulator of the actin cytoskeleton, may confer virulence properties on S. aureus. In this study, for the first time, analysis of S. aureus strains, recovered in DFIs at an initial stage and during the follow-up, showed that 71.4% of edin-positive strains were associated with moderate-to-severe infections (grades 3 and 4 of the IDSA/IWGDF classification) compared with 28.6% of edin-positive strains associated with low-grade infections. Most of these strains were edin-B positive (86.7%) and belonged to CC25/28-MSSA (n = 10). One edin-B-positive ST152-MSSA strain was negative for the two highly prevalent predictive markers of infecting strains (lukDE and hlgv). Collectively, this points towards the edin-B encoding gene as a bonafide subsidiary predictive risk marker of DFI.     

Virulence factors and genotypes of Staphylococcus aureus from infection and carriage in Gabon

Staphylococcus aureus isolates from developed countries have been extensively analyzed with respect to their virulence patterns and clonal relatedness but there is only sparse information on the molecular diversity of S. aureus isolates from Africa. In particular, little is known about S. aureus isolates from asymptomatic carriers compared with isolates causing infections. From 2008 to 2010, we prospectively collected S. aureus isolates from asymptomatic carriers and infections in Lambaréné, Gabon, Central Africa. For these isolates, we determined major virulence factors, and performed multilocus sequence typing (MLST) and spa typing. Among 163 S. aureus isolates from asymptomatic carriers, we found the MLST clonal complexes (CCs) 5, 6, 7, 8, 9, 15, 25, 30, 45, 88, 101, 121 and 152; 3.7% were methicillin-resistant (MRSA). The clinical isolates were associated with CCs 5, 8, 9, 15, 88, 121 and 152; 11% were MRSA. Sequence types 1 and 88 were significantly associated with infection and sequence type 508 was associated with carriage. Remarkably, there was a high prevalence of Panton–Valentine leukocidin (PVL) -encoding genes both in disease-related isolates (57.4%) and in carrier isolates (40.5%). We found differences in the clonal structure and virulence pattern of Gabonese S. aureus isolates from asymptomatic carriers and infections. Of note, S. aureus isolates from Gabon show a very high prevalence of PVL-encoding genes, which exceeds the rates observed for developed countries.     

Molecular fingerprinting of Staphylococcus aureus from bone and joint infections

The objective of the study was to determine if a clonal complex (CC) of Staphylococcus aureus or certain virulence and adhesion factors were associated with infections of bones and prosthetic implants. One hundred and nineteen isolates were characterised using microarrays. There was no evidence for a single virulence factor or CC being causative for bone and implant infections. Isolates belonged to 20 different CCs, with CC8 (19.33%), CC45 (17.65%) and CC30 (12.61%) being dominant. Population structure and the relative abundances of virulence genes was similar to previously described isolates from healthy carriers. Differences to carrier isolates included a higher proportion of CC45, a lower proportion of CC15, as well as a higher abundance of sak (staphylokinase) among patient isolates. For 23 patients with infections of total knee or hip prosthetics, it was possible to simultaneously obtain nasal swabs. Fifteen (65.2%) carried S. aureus in their anterior nares. In nine of them (39.1%), isolates from the infection site were identical to carriage isolates. This suggests an elevated risk of infection for S. aureus carriers and the possibility of endogenous infection in a high proportion of them. Therefore, the pre-operative screening and eradication of S. aureus in patients receiving total joint prosthetics should be considered.     

Molecular characteristics of Staphylococcus aureus associated with chronic rhinosinusitis

The anterior nares have been regarded as the major carriage site of Staphylococcus aureus. From here, the organism can spread to other parts of the body where it might act as harmless commensal or cause mild to severe infections. Nasal sinuses are normally sterile, but in patients with chronic rhinosinusitis (CRS), the finding of S. aureus in maxillary sinus cultures is common. Isolates were obtained from the nares and maxillary sinus of patients with CRS and the nares of healthy controls. A significantly higher frequency of S. aureus was found in nares samples from patients (24/42) compared to controls (16/57) (p = 0.004). There is no consensus regarding whether S. aureus is a relevant pathogen in CRS. A DNA microarray was used to investigate the prevalence of S. aureus virulence genes with focus on staphylococcal enterotoxins, toxic shock syndrome toxin‐1, agr types, and cell wall‐associated proteins. The genotyping of S. aureus isolates revealed only small and non‐significant differences in gene prevalence between isolates collected from patients with CRS and those collected from healthy nasal carriers. This study provides an increased knowledge of the genetic pattern of virulence genes among S. aureus collected in CRS.     

Cytotoxic effects of ingested Staphylococcus aureus on bovine endothelial cells: Role of S. aureus α-hemolysin

Previously we observed that Staphylococcus aureus phagocytized by cultured bovine endothelial cells do not proliferate intracellularly, but are cytotoxic to bovine endothelial cells. To investigate S. aureus virulence factors which may be produced intracellularly and cause lysis of endothelial cells, we tested S. aureus mutants defective in production of one or more potential virulence factors and corresponding parent strains for cytotoxicity to endothelial cell monolayers subsequent to being ingested. Following incubation of endothelial cell monolayers with S. aureus for 3.5 h, cultures were supplemented with lysostaphin to destroy extracellular but not intracellular S. aureus. At subsequent times, viability of endothelial cells was assayed by retention of ³H-adenine and the number of intracellular S. aureus was measured. The cytotoxic activity of S. aureus culture supernatants was also characterized. The results indicate that S. aureus α-hemolysin is cytotoxic to bovine endothelial cells and plays an important role in the damage suffered by bovine endothelial cell monolayers following ingestion of S. aureus. Ingestion of α-hemolysin-producing S. aureus by endothelial cells in vivo might be expected to result in destruction of endothelium followed by development of platelet-fibrin vegetations. This possible sequence of events is compatible with the frequently fulminant course of S. aureus endocarditis.     

Genetic diversity and antimicrobial resistance of Staphylococcus aureus from recurrent tonsillitis in children

The aim of this study was to analyze the prevalence of Staphylococcus aureus in the tonsils of children subjected tonsillectomy due to recurrent tonsilitis and to determine the spa types of the pathogens, carriage of virulence genes and antimicrobial resistance profiles. The study included 73 tonsillectomized children. Bacteria, including S. aureus were isolated from tonsillar surface prior to tonsillectomy, recovered from tonsillar core at the time of the surgery, and from posterior pharynx 2–4 weeks after the procedure. Staphylococcus aureus isolates were compared by spa typing, tested for antimicrobial susceptibility and for the presence of superantigenic toxin genes (sea-seu, eta, etb, tst, lukS/lukF-PV) by multiplex polymerase chain reaction. Seventy-three patients (mean 7.1 ± 4.1 years, 61.6% male) were assessed. The most commonly isolated bacteria were S. aureus. The largest proportion of staphylococcal isolates originated from tonsillar core (63%), followed by tonsillar surface (45.1%) and posterior pharynx in tonsillectomized children (18.2%, p = 0.007). Five (6.3%) isolates were identified as MRSA (mecA-positive). Up to 67.5% of the isolates synthesized penicillinases (blaZ-positive isolates), and 8.8% displayed MLS_B resistance. The superantigenic toxin genes were detected in more than half of examined isolates (56.3%). spa types t091, t084, and t002, and clonal complexes (CCs) CC7, CC45, and CC30 turned out to be most common. Staphylococcus aureus associated with RT in children showed pathogenicity potential and considerable genetic diversity, and no clones were found to be specific for this condition although further studies are needed.     

Forte prévalence des infections communautaires et nosocomiales à Staphylococus aureus résistant à la méticilline et portant le gène de la leucocidine de Panton-Valentine dans l’Algérois

Objectives

To determine the prevalence of community acquired and hospital methicillin-resistant Staphylococcus aureus (S. aureus) infections and the Panton-Valentine leukocidin.

Patients and methods

Seven hundred S. aureus strains were collected during 21 months period in Mustapha Bacha hospital. Bacterial identification was based on standard methods and susceptibilities were tested by disk diffusion method. Molecular study (toxins, mecA gene and agr alleles) were determined for 221 S. aureus isolates by multiplex PCR.

Results

The global MRSA prevalence was 42 %, 35 % in the community and 49 % in hospital setting. The frequency of strains containing PVL genes (PVL+) was 36 %, their molecular profile was: agr3, mecA+, etd, edin, which correspond to the C-MRSA major ST80 clone in Europe and the Maghreb. The H-MRSA-PVL+ were multidrug resistant. Among the MSSA, 13 strains contained the tst gene and five contained the exfoliatine genes ETA and ETB.

Conclusion

Our results show a high rate of MRSA-PVL+ in the community and the hospital setting. The H-MRSA-PVL+ were multidrug resistant complicating their antibiotic treatment options.     

Molecular characterization of Staphylococcus aureus from outpatients in the Caribbean reveals the presence of pandemic clones

Staphylococcus aureus infections continue to pose a global public health problem. Frequently, this epidemic is driven by the successful spread of single S. aureus clones within a geographic region, but international travel has been recognized as a potential risk factor for S. aureus infections. To study the molecular epidemiology of S. aureus infections in the Caribbean, a major international tourist destination, we collected methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) isolates from community-onset infections in the Dominican Republic (n = 112) and Martinique (n = 143). Isolates were characterized by a combination of pulsed-field gel electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST) typing. In Martinique, MRSA infections (n = 56) were mainly caused by t304-ST8 strains (n = 44), whereas MSSA isolates were derived from genetically diverse backgrounds. Among MRSA strains (n = 22) from the Dominican Republic, ST5, ST30, and ST72 predominated, while ST30 t665-PVL+ (30/90) accounted for a substantial number of MSSA infections. Despite epidemiological differences in sample collections from both countries, a considerable number of MSSA infections (~10%) were caused by ST5 and ST398 isolates at each site. Further phylogenetic analysis suggests the presence of lineages shared by the two countries, followed by recent genetic diversification unique to each site. Our findings also imply the frequent import and exchange of international S. aureus strains in the Caribbean.     

Analysis of Staphylococcus aureus proteins secreted inside infected human epithelial cells

Staphylococcus aureus, an opportunistic pathogen is able to invade into and persist inside non-professional phagocytic cells. To do so, this bacterium possesses a wide range of secreted virulence factors which enable attachment to the host as well as intracellular survival. Hence, a monitoring of virulence factors specifically produced upon internalization might reveal targets for prevention or therapy of S. aureus infections. However, previous proteome approaches enriching S. aureus from lysed host cells after infection did not cover secreted virulence factors.Therefore, we used density gradient centrifugation and mass spectrometry to identify S. aureus HG001 proteins which were secreted into compartments of infected human bronchial epithelial S9 cells. Because shotgun mass spectrometry revealed only few bacterial proteins amongst 1905 host proteins, we used highly sensitive and selective single reaction monitoring mass spectrometry as an alternative approach and quantified 37 bacterial proteins within the S. aureus containing host cell compartment 2.5 h and 6.5 h post infection. Among them were secreted bacterial virulence factors like lipases, pore forming toxins, and secreted adhesins which are usually hard to detect from infected sample material by proteomics approaches due to their low abundance. S. aureus adapted its proteome to improve its response to oxidative and cell wall stress occurring inside the host, but also, increased the amounts of some adhesins and pore-forming toxins, required for attachment and host cell lysis.     

Global spread of mouse-adapted Staphylococcus aureus lineages CC1, CC15, and CC88 among mouse breeding facilities

We previously reported that laboratory mice from all global vendors are frequently colonized with Staphylococcus aureus (S. aureus). Genotyping of a snap sample of murine S. aureus isolates from Charles River, US, showed that mice were predominantly colonized with methicillin-sensitive CC88 strains. Here, we expanded our view and investigated whether laboratory mice from other global animal facilities are colonized with similar strains or novel S. aureus lineages, and whether the murine S. aureus isolates show features of host adaptation. In total, we genotyped 230 S. aureus isolates from various vendor facilities of laboratory mice around the globe (Charles River facilities in the USA, Canada, France, and Germany; another US facility) and university- or company-associated breeding facilities in Germany, China and New Zealand. Spa typing was performed to analyse the clonal relationship of the isolates. Moreover, multiplex PCRs were performed for human-specific virulence factors, the immune-evasion cluster (IEC) and superantigen genes (SAg). We found a total of 58 different spa types that clustered into 15 clonal complexes (CCs). Three of these S. aureus lineages had spread globally among laboratory mice and accounted for three quarters of the isolates: CC1 (13.5%), CC15 (14.3%), and CC88 (47.0%). Compared to human colonizing isolates of the same lineages, the murine isolates frequently lacked IEC genes and SAg genes on mobile genetic elements, implying long-term adaptation to the murine host. In conclusion, laboratory mice from various vendors are colonized with host-adapted S. aureus-strains of a few lineages, predominantly the CC88 lineage. S. aureus researchers must be cautioned that S. aureus colonization might be a relevant confounder in infection and vaccination studies and are therefore advised to screen their mice before experimentation.     

Methicillin‐resistant and vancomycin‐intermediate Staphylococcus aureus colonizing patients and intensive care unit environment: virulence profile and genetic variability

This study aims to determine the prevalence of Staphylococcus aureus colonizing patients and ICU environment of a teaching hospital, the virulence and antimicrobial susceptibility profile of the isolates, and to evaluate the genetic relationship among them. A total of 536 swabs (134 of patients and 402 of ICU environment) were collected and analyzed to detect S. aureus. The antimicrobial susceptibility of the isolates was determined by disk diffusion test, and the detection of the mecA and virulence factors genes was performed by PCR, in addition to SCCmec typing. The genetic similarity of the isolates was determined by PFGE. Staphylococcus aureus was isolated in 12.7% of the swabs. The prevalence of colonization was 13.4% in patients and 12.4% in the environmental samples. The multidrug resistance was determined in 82.4% of the isolates. The prevalence of methicillin‐resistant S. aureus was 20.6%, with 50.0% classified as SCCmec IV. The intermediate resistance to vancomycin was detected in 5.9% and 4.4% of the isolates obtained from patients and environment, respectively. Identical isolates obtained from different patients and sources were grouped into several clusters. The results showed dissemination of multidrug‐resistant strains between patients and fomites and the persistence of MRSA and VISA isolates in the ICU environment.     

Nasal carriage of Staphylococcus aureus in healthy humans with different levels of contact with animals in Tunisia: genetic lineages, methicillin resistance, and virulence factors

Nasal swabs of 423 healthy humans who showed different levels of contact with animals (frequent, 168; sporadic, 94; no contact, 161) were obtained in Tunisia (2008–2009), and 99 of them presented other associated risk factors. Methicillin-resistant Staphylococcus aureus (MRSA) was detected in one of these 423 samples (0.24%), retrieved from a veterinarian. The MRSA isolate was mecA-positive, typed as ST80-t203-SCCmecIVc-agrIII, and contained tet(K), ant(6)-Ia, and aph(3′)-IIIa genes encoding tetracycline, streptomycin, and kanamycin resistance, respectively. This MRSA isolate also contained the lukF/lukS virulence gene encoding Panton–Valentine leukocidin. Fifty-four (12.8%) additional nasal samples contained methicillin-susceptible S. aureus (MSSA) and one isolate/sample was characterized. A high diversity of spa types (n = 43; 4 new) and pulsed-field gel electrophoresis (PFGE) types (n = 37) was detected among the 55 recovered S. aureus strains. The percentages of antimicrobial resistance/detected resistance genes were as follows: tetracycline [22%/tet(K)-tet(L)-tet(M)], erythromycin [5%/msrA], ciprofloxacin [14.5%], trimethoprim–sulfamethoxazole [2%/dfrA], streptomycin [11%/ant(6)-Ia], kanamycin [7%/aph(3′)-IIIa], amikacin [5%], and chloramphenicol [2%]. Four and two isolates carried the lukF/lukS and eta and/or etb genes, respectively, and always in individuals with contact with animals. Eleven isolates carried the tst gene and were recovered from individuals with different levels of contact with animals.     

The presence of both bone sialoprotein-binding protein gene and collagen adhesin gene as a typical virulence trait of the major epidemic cluster in isolates from orthopedic implant infections

Staphylococcus aureus is a major, highly clonal, pathogen causing implant infections. This study aimed at investigating the diverse distribution of bacterial adhesins in most prevalent S. aureus strain types causing orthopaedic implant infections. 200 S. aureus isolates, categorized into ribogroups by automated ribotyping, i.e. rDNA restriction fragment length polymorphism analysis, were screened for the presence of a panel of adhesins genes. Within the collection of isolates, automated ribotyping detected 98 distinct ribogroups. For many ribogroups, characteristic tandem genes arrangements could be identified. In the predominant S. aureus cluster, enlisting 27 isolates, the bbp gene encoding bone sialoprotein-binding protein appeared a typical virulence trait, found in 93% of the isolates. Conversely, the bbp gene was identified in just 10% of the remaining isolates of the collection. In this cluster, co-presence of bbp with the cna gene encoding collagen adhesin was a pattern consistently observed. These findings indicate a crucial role of both these adhesins, able to bind the most abundant bone proteins, in the pathogenesis of orthopaedic implant infections, there where biomaterials interface bone tissues. This study suggests that specific adhesins may synergistically act in the onset of implant infections and that anti-adhesin strategies should be targeted to adhesins conjointly present.     

Comparison of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> isolates associated with food intoxication with isolates from human nasal carriers and human infections

Staphylococcus aureus represents an organism of striking versatility. While asymptomatic nasal colonization is widespread, it can also cause serious infections, toxinoses and life-threatening illnesses in humans and animals. Staphylococcal food poisoning (SFP), one of the most prevalent causes of foodborne intoxication worldwide, results from oral intake of staphylococcal enterotoxins leading to violent vomiting, diarrhea and cramps shortly upon ingestion. The aim of the present study was to compare isolates associated with SFP to isolates collected from cases of human nasal colonization and clinical infections in order to investigate the role of S. aureus colonizing and infecting humans as a possible source of SFP. Spa typing and DNA microarray profiling were used to characterize a total of 120 isolates, comprising 50 isolates collected from the anterior nares of healthy donors, 50 isolates obtained from cases of clinical infections in humans and 20 isolates related to outbreaks of staphylococcal food poisoning. Several common spa types were found among isolates of all three sources (t015, t018, t056, t084). DNA microarray results showed highly similar virulence gene profiles for isolates from all tested sources. These results suggest contamination of foodstuff with S. aureus colonizing and infecting food handlers to represent a source of SFP.     

Molecular Characterization of Endocarditis-Associated Staphylococcus aureus

Infective endocarditis (IE) is a life-threatening infection of the heart endothelium and valves. Staphylococcus aureus is a predominant cause of severe IE and is frequently associated with infections in health care settings and device-related infections. Multilocus sequence typing (MLST), spa typing, and virulence gene microarrays are frequently used to classify S. aureus clinical isolates. This study examined the utility of these typing tools to investigate S. aureus epidemiology associated with IE. Ninety-seven S. aureus isolates were collected from patients diagnosed with (i) IE, (ii) bloodstream infection related to medical devices, (iii) bloodstream infection not related to medical devices, and (iv) skin or soft-tissue infections. The MLST clonal complex (CC) for each isolate was determined and compared to the CCs of members of the S. aureus population by eBURST analysis. The spa type of all isolates was also determined. A null model was used to determine correlations of IE with CC and spa type. DNA microarray analysis was performed, and a permutational analysis of multivariate variance (PERMANOVA) and principal coordinates analysis were conducted to identify genotypic differences between IE and non-IE strains. CC12, CC20, and spa type t160 were significantly associated with IE S. aureus. A subset of virulence-associated genes and alleles, including genes encoding staphylococcal superantigen-like proteins, fibrinogen-binding protein, and a leukocidin subunit, also significantly correlated with IE isolates. MLST, spa typing, and microarray analysis are promising tools for monitoring S. aureus epidemiology associated with IE. Further research to determine a role for the S. aureus IE-associated virulence genes identified in this study is warranted.     

High prevalence of ST121 in community-associated methicillin-susceptible Staphylococcus aureus lineages responsible for skin and soft tissue infections in Portuguese children

In order to evaluate the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in Portugal, we analyzed a collection of 38 S. aureus isolates recovered from 30 children attending the pediatric emergency department of a central hospital in Lisbon due to skin and soft tissue infections. Molecular characterization identified seven clonal lineages among the 35 methicillin-susceptible S. aureus (MSSA) isolates, of which the major lineage PFGE A/t159/ST121 included 63% of the isolates. The three MRSA isolates belonged to the Pediatric clone PFGE D/t535/ST5-IV (n = 2) and to the European CA-MRSA clone PFGE G/t044/ST80-IVc (n = 1). All isolates harbored several virulence factors, namely, leukocidins. Panton–Valentine leukocidin (PVL) was produced by isolates from five MSSA lineages and by the ST80 MRSA. Of interest, this is the first reported isolation of CA-MRSA ST80 in Portugal.     

Panton-Valentine Leukocidin-Positive Staphylococcus aureus in Ireland from 2002 to 2011: 21 Clones,Frequent Importation of Clones,Temporal Shifts of Predominant Methicillin-Resistant S. aureus Clones,and Increasing Multiresistance

There has been a worldwide increase in community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) infections. CA-MRSA isolates commonly produce the Panton-Valentine leukocidin toxin encoded by the pvl genes lukF-PV and lukS-PV. This study investigated the clinical and molecular epidemiologies of pvl-positive MRSA and methicillin-susceptible S. aureus (MSSA) isolates identified by the Irish National MRSA Reference Laboratory (NMRSARL) between 2002 and 2011. All pvl-positive MRSA (n = 190) and MSSA (n = 39) isolates underwent antibiogram-resistogram typing, spa typing, and DNA microarray profiling for multilocus sequence type, clonal complex (CC) and/or sequence type (ST), staphylococcal cassette chromosome mec type assignment, and virulence and resistance gene detection. Where available, patient demographics and clinical data were analyzed. The prevalence of pvl-positive MRSA increased from 0.2% to 8.8%, and that of pvl-positive MSSA decreased from 20% to 2.5% during the study period. The pvl-positive MRSA and MSSA isolates belonged to 16 and 5 genotypes, respectively, with CC/ST8-MRSA-IV, CC/ST30-MRSA-IV, CC/ST80-MRSA-IV, CC1/ST772-MRSA-V, CC30-MSSA, CC22-MSSA, and CC121-MSSA predominating. Temporal shifts in the predominant pvl-positive MRSA genotypes and a 6-fold increase in multiresistant pvl-positive MRSA genotypes occurred during the study period. An analysis of patient data indicated that pvl-positive S. aureus strains, especially MRSA strains, had been imported into Ireland several times. Two hospital and six family clusters of pvl-positive MRSA were identified, and 70% of the patient isolates for which information was available were from patients in the community. This study highlights the increased burden and changing molecular epidemiology of pvl-positive S. aureus in Ireland over the last decade and the contribution of international travel to the influx of genetically diverse pvl-positive S. aureus isolates into Ireland.     

Development of a vaccine against <Emphasis Type="Italic">Staphylococcus aureus</Emphasis>

A vaccine to prevent infections caused by Staphylococcus aureus would have a tremendously beneficial impact on public health. In contrast to typical encapsulated bacterial pathogens, such as Streptococcus pneumoniae, H. influenzae, and Neisseria meningitides, the capsule of S. aureus is not clearly linked to strain virulence in vivo. Furthermore, it is not clear that natural infection caused by S. aureus induces a protective humoral immune response, as does infection caused by typical encapsulated bacteria. Finally, pure B cell or antibody deficiency, in either animal models or in patients, does not predispose to more frequent or more severe S. aureus infections, as it does for infections caused by typical encapsulated bacteria. Rather, primary immune mechanisms necessary for protection against S. aureus infections include professional phagocytes and T lymphocytes (Th17 cells, in particular) which upregulate phagocytic activity. Thus, it is not clear whether an antibody-mediated neutralization of S. aureus virulence factors should be the goal of vaccination. Rather, the selection of antigenic targets which induce potent T cell immune responses that react to the broadest possible array of S. aureus strains should be the focus of antigen selection. Of particular promise is the potential to select antigens which induce both humoral and T cell-mediated immunity in order to generate immune synergy against S. aureus infections. A single-antigen vaccine may achieve this immune synergy. However, multivalent antigens may be more likely to induce both humoral and T cell immunity and to induce protection against a broader array of S. aureus isolates. A number of candidate vaccines are in development, raising the promise that effective vaccines against S. aureus will become available in the not-so-distant future. Possible development programs for such vaccines are discussed.     

Microcins and urovirulence in Escherichia coli

Urinary tract infections are among the most common infectious diseases encountered in humans and Escherichia coli is their leading etiologic agent. Uropathogenic E. coli encompasses a group of bacteria possessing a variable virulence gene assortment. It is generally agreed that many urovirulence factors remain to be discovered and that this information is required to gain knowledge on the pathogenic processes underlying the different clinical presentations of urinary tract infections. The production of higher-molecular-mass microcins, a group of ribosomally-synthesized peptide antibiotics comprising microcins H47, I47, E492, M and ColV, has been proposed as a virulence trait of some uropathogenic E. coli. To study this possibility, clones producing any of these microcins were selected from a collection of 160 Gram-negative clinical isolates from urine cultures and their virulence profile was analyzed. The study consisted in surveying genetic loci known to be relevant to urinary tract infection caused by E. coli. Depending on the type of microcin produced, different virulence patterns were observed which seemed to be determined by the degree of compatibility between virulence and microcin loci. In conclusion, results pointed to a relationship between higher-molecular-mass microcins and urovirulence.