The functionalibility of these genes has been experimentally demonstrated for pNL1, as this plasmid has been conjugatively transferred among different sphingomonads. In contrast, this website no experimental evidence for a conjugative transfer of plasmid pCAR3 could be demonstrated (Romine et al., 1999; Shintani et al., 2007). Also plasmid pSWIT02 (which also belongs to the ‘Mega-RepAC-group’)

carries genes coding for conjugative functions, but these genes had been annotated as vir genes. The annotated sequence of plasmid pSWIT02 suggested that this vir-operon consisted of the genes virB1–virB11 (NCBI registry numbers ABQ71617–ABQ71626). The organization of these genes is identical to the organization of the homologous genes on the Ti plasmid from A. tumefaciens and the Tra-systems of broad-host-range plasmids belonging to the IncN and IncW incompatibility groups. In addition, also the gene encoding the ‘coupling protein’ VirD4 could be identified in direct neighbourhood to the vir genes. Thus, on plasmid pSWIT02, all genes are present which allow the conjugative

transfer of broad-host-range plasmids. The absence/presence of certain genes and also the organization of conserved genes suggested that the conjugative system of plasmid pSWIT02 is different to that of plasmids pNL1 and pCAR3. Thus, the conjugative systems from plasmids pNL1 and pCAR3 are closer related to the system present on the F-plasmid, and the transfer functions encoded by plasmid

pSWIT02 are closer related to the Ti plasmid or the IncN/IncW plasmids. The plasmids belonging to the ‘Mega-Rep3-group’ (pCHQ1, pSLCP, pSPHCH01, pISP0, pLA1) all seem to carry a learn more full set of conjugative genes. The respective gene clusters had been annotated for plasmids pISP0, pSLPG, pSPHCH01 as vir genes, and all required genes (virB1–virB11, virD2 and virD4 with some exceptions regarding virB7) have been annotated. In contrast, on plasmids pCHQ1 and pLA1, the isofunctional genes had been annotated as trb or tra genes. Furthermore, the respective gene clusters from pCHQ1 and pLA1 also included traW, traU/trbC, traN, traF, traH, traG, which are specifically found in plasmids related to the F-plasmid and which do not have homologous genes in the vir-operon Racecadotril (Lawley et al., 2004). Significant differences in the conjugative systems are also observed for the plasmids belonging to the ‘Mega-RPA-group’. Thus, plasmid pISP1 carries a large cluster of tra genes (traL, traE, traK, traB, traC, traW, traU, traN, traF, traH, traG, traI, traH; NCBI registry numbers YP_007618159–YP_0076181751617). These tra genes show the same organization as those found on plasmids pNL1 and pCAR3 (and also the F-plasmid). In contrast, the two other plasmids from this group (pNL2 and Mpl) do not code for ‘conjugative genes’. It is conspicuous that these plasmids are the largest sequenced plasmids from sphingomonads (pNL2 = 487 kb; Mpl = 1160 kb).

These new recombinant forms may reflect the diversification of the HIV-1 epidemic in this country, as a result of both migration from neighbouring countries and recombination events within the local population. This increasing diversity could lead to the emergence of new resistance pathways that could affect first-line

therapy in the future. Several studies have suggested that non-B isolates show a different pattern of resistance mutations from subtype B [10,11]. Reports have shown that the mutation V106M confers resistance to NNRTIs in subtype C HIV [12], and is preferentially selected in vivo [13], and that the D30N mutation is not preferentially selected in HIV-1 Venetoclax subtype C in the development of resistance to nelfinavir [14]. We have previously shown that subtype K reverse transcriptase may preferentially select for the thymidine analogue mutation 2 (TAM-2) pathways in the presence of NRTIs [15]. Differences in the way in which resistance evolves among subtypes may mean that some second-line regimens will be less effective than previously thought. Moreover, treatment of patients with primary resistance will be compromised from the U0126 nmr outset, potentially leading to onward transmission of drug-resistant HIV. Use of compromised treatment regimens may not result in the expected prevention benefits; that is, decreased HIV transmission. The

World Health Organization (WHO) currently recommends first-line therapy with two NRTIs and one NNRTI, a combination with high efficacy, tolerability and simplicity and low cost, and showing high adherence to treatment [16]. First-line regimens in Mali are based on this recommendation. Antiretroviral drugs have been made available in Mali

since 1997, and have been free since 2004. The recommended first-line regimen is a fixed-dose combination of stavudine/lamivudine/nevirapine, currently prescribed free of charge for the majority of patients. The alternative first-line regimens are zidovudine/lamivudine/efavirenz and zidovudine/lamivudine/nevirapine. The recommended second-line regimen is abacavir/didanosine/indinavir, and the alternative drugs are tenofovir Buspirone HCl and lopinavir [7] or indinavir/ritonavir. An increase in the prevalence of primary resistance could jeopardize these second-line options. The availability of antiretrovirals has brought great hope to HIV-infected individuals in resource-limited countries. The emergence and transmission of resistant virus could compromise the effectiveness of specific treatments in areas where therapeutic options are limited [17]. There were limited data on primary antiretroviral drug resistance before 2000 in these countries [18]. Preliminary data suggest that resistance may be emerging in countries currently scaling up access to antiretroviral therapy [19]. Data from Africa support this suggestion.

burnetii Doramapimod strain

(RSA493) Nine Mile phase I genomic sequence, which revealed a set of genes with significant homology to the Dot/Icm type IVB secretion system (T4BSS) of Legionella pneumophila. In L. pneumophila, the T4BSS system consists of 26 ORFs, of which 23 share significant homology with C. burnetii ORFs (Seshadri et al., 2003). Studies show that the L. pneumophila T4BSS is required for intracellular survival, effector protein secretion, and replication within host cells (Marra et al., 1992; Berger & Isberg, 1993; Vogel et al., 1998; Bruggemann et al., 2006; Ninio & Roy, 2007; Kubori et al., 2008; Shin & Roy, 2008), thus playing a vital role in the infectious process of L. pneumophila. Moreover, the genome sequence revealed C. burnetii ORFs containing eukaryotic Ankyrin-binding repeat domains (Pan et al., 2008; Voth et al., 2009). Subsequently, these ORFs were shown to be secreted by L. pneumophila in a T4BSS-dependent manner (Pan et al., 2008; Voth et al., 2009), further implicating

the C. burnetii T4BSS as a significant contributor to cellular pathogenesis, BYL719 and yet characterization of the T4BSS structure in C. burnetii is lacking. In general, T4SS serve to export virulence factors, which include nucleoprotein complexes and effector proteins, into a host or into the extracellular milieu (Christie & Vogel, 2000; Sexton & Vogel, 2002; Cascales & Christie, 2003). T4SS have been subdivided into two families: (1) the VirB/D4 (T4ASS) and (2) the Dot/Icm (T4BSS) systems (Christie & Vogel, 2000).

The T4ASS of Agrobacterium tumefaciens directly injects effector molecules into adjacent cells (Christie ADP ribosylation factor & Vogel, 2000) as well as into the extracellular environment (Dillard & Seifert, 2001; Hofreuter et al., 2001). Interestingly, VirB8, part of the core complex, was reported to localize at the pole of A. tumefaciens cells (Kumar et al., 2000), and the bacterium attaches to host plant cells perpendicular to the bacterial poles (Matthysse, 1987). In L. pneumophila, the T4BSS is essential for cellular pathogenesis via secretion of effector proteins into a host cell (Sexton & Vogel, 2002; Christie et al., 2005). In L. pneumophila, the T4BSS component, DotF, appears to demonstrate polar localization (Jeong et al., 2006). Virulence factors localize or are dispersed about the pole(s) of a wide range of bacteria, and include alternate secretion systems, effector protein molecules, and surface membrane-associated proteins. Evidence suggests that the T3SS of Shigella flexneri is present at the poles of the bacteria before the secretion of IpaC (Jaumouille et al., 2008). Recently, the Mycobacterium marinum Esx-1 T7SS was shown to secrete Mh3864 at the poles and that a core Esx-1 component, Mh3870, localized preferentially to the poles (Carlsson et al., 2009).

The characteristics of the patient, conditions, treatments, type of unit in the foreign hospital, high-risk setting of initial hospital unit, time to repatriation, and modalities of the transfer were abstracted from the electronic medical record of MAF. Follow-up determinations were made, consisting of collection and review of the discharge

summary from the French hospital. The Committee for Protection of Persons waived the requirement for patient’s consent; nonetheless, we determined that all study patients were not opposed to the use of their data for a scientific purpose. All the patients and provider identities were blinded in all aspects. To more specifically describe the population, patients who clearly Selleckchem Sirolimus underwent MRB detection were allocated to one of two groups: those with MRB detected after testing at their arrival in the French hospital and those found to be negative for MRB. Data were expressed as mean ± SD, or median (interquartile range) and percentage of patients; these descriptive data were compared between the two groups. Statistical analysis was performed by non-parametric tests for quantitative data and a Fisher exact

test for qualitative data. We used statistical package Stat-View 5 (Abacus Concept, Berkeley, CA, USA). Among 248 patients who met inclusion criteria, 7 patients were excluded because they were involved in armed conflicts with uncertain initial care in the foreign hospital. Demographic and other Bortezomib mw basic descriptive data were determined for the 241 patients. Mean age was 55 ± 21 years with 54% male gender. The primary

diagnostic groups included trauma (40%), cardiac (15%), neurologic (12%), and respiratory (7%). Geographic locations are shown in Figure 1a and b, consisting of Europe (44%), North Africa (22%), sub-Saharan Africa (12%), and Asia (12%). During their stay in the foreign hospital, 85 patients presented with infectious syndromes (34%) and 86 received antibiotics (35%). One-hundred sixteen (48%) patients were admitted to a high-risk unit. The median stay before their international inter-facility transfer was 7 days with an interquartile range of 4 to 10 days. Of the total included population, for 18 patients, the hospital into which the Protein Tyrosine Kinase inhibitor patient was admitted refused to collaborate. The remaining 223 patients represent the study population analyzed. When admitted in France, 16 patients were identified as having MRB colonization (7%). Of the 207 patients who were not positive for MRB, 32 patients were clearly determined as non-MRB carriers after appropriate testing. The characteristics of MRB carriers as compared with confirmed non-MRB patients are presented in Table 1. The duration of foreign hospital stay was significantly longer in MRB carriers compared with confirmed non-MRB patients [13 (3–20) vs 8 (6–14) d, p = 0.

The characteristics of the patient, conditions, treatments, type of unit in the foreign hospital, high-risk setting of initial hospital unit, time to repatriation, and modalities of the transfer were abstracted from the electronic medical record of MAF. Follow-up determinations were made, consisting of collection and review of the discharge

summary from the French hospital. The Committee for Protection of Persons waived the requirement for patient’s consent; nonetheless, we determined that all study patients were not opposed to the use of their data for a scientific purpose. All the patients and provider identities were blinded in all aspects. To more specifically describe the population, patients who clearly Idasanutlin cost underwent MRB detection were allocated to one of two groups: those with MRB detected after testing at their arrival in the French hospital and those found to be negative for MRB. Data were expressed as mean ± SD, or median (interquartile range) and percentage of patients; these descriptive data were compared between the two groups. Statistical analysis was performed by non-parametric tests for quantitative data and a Fisher exact

test for qualitative data. We used statistical package Stat-View 5 (Abacus Concept, Berkeley, CA, USA). Among 248 patients who met inclusion criteria, 7 patients were excluded because they were involved in armed conflicts with uncertain initial care in the foreign hospital. Demographic and other Selleck Small molecule library basic descriptive data were determined for the 241 patients. Mean age was 55 ± 21 years with 54% male gender. The primary

diagnostic groups included trauma (40%), cardiac (15%), neurologic (12%), and respiratory (7%). Geographic locations are shown in Figure 1a and b, consisting of Europe (44%), North Africa (22%), sub-Saharan Africa (12%), and Asia (12%). During their stay in the foreign hospital, 85 patients presented with infectious syndromes (34%) and 86 received antibiotics (35%). One-hundred sixteen (48%) patients were admitted to a high-risk unit. The median stay before their international inter-facility transfer was 7 days with an interquartile range of 4 to 10 days. Of the total included population, for 18 patients, the hospital into which the Alanine-glyoxylate transaminase patient was admitted refused to collaborate. The remaining 223 patients represent the study population analyzed. When admitted in France, 16 patients were identified as having MRB colonization (7%). Of the 207 patients who were not positive for MRB, 32 patients were clearly determined as non-MRB carriers after appropriate testing. The characteristics of MRB carriers as compared with confirmed non-MRB patients are presented in Table 1. The duration of foreign hospital stay was significantly longer in MRB carriers compared with confirmed non-MRB patients [13 (3–20) vs 8 (6–14) d, p = 0.

The distribution of single etiological diagnoses differed significantly

between older and younger travelers, as shown in Table 3. Lower respiratory tract infections (LRTIs), high-altitude pulmonary edema (HAPE), arthropod bites, Plasmodium falciparum severe malaria, rickettsiosis, gastritis, peptic ulcer, esophagitis and gastroesophageal reflux disease (GERD), LY2109761 strongyloÏdes, trauma and injuries, altitude illness, vertigo, cerebrovascular accident, urinary tract infections (UTIs), heart disease, phlebitis, pulmonary embolism, and death were more frequently observed in older GeoSentinel patients compared to their younger counterparts. Deaths in young and older travelers were mainly caused by infectious diseases. In contrast, acute bacterial and parasitic diarrhea, upper

respiratory tract infections (URTI), flu and flu-like illnesses, larva migrans, dengue, non-severe P falciparum and non-P falciparum malaria, salmonella infections, genital infections and sexually transmitted diseases, and schistosomiasis were comparatively less frequently diagnosed in the older group. Illnesses observed in more than 45 patients per age group were further investigated for potential confounders such as sex, reason for travel, travel duration and region of travel, pre-travel advice, clinical settings, and risk Lumacaftor level qualifier. We found that age per se was associated with the distinct patterns of travel-associated illness observed in older and younger individuals in all cases with the exception of high-altitude cerebral edema, acute mountain sickness, and strongyloÏdes (Figure 1).

Subanalysis in the older group by age category showed a linear positive relationship Rebamipide between age and the relative proportion of death, heart disease, and LRTI, and an inverse relationship between age and P falciparum malaria and dengue among ill travelers, with all trends being significant (p < 0.001) (Figure 2). Among ill adult travelers seen at GeoSentinel clinics, individuals over 60 years of age represent a substantial proportion of patients, and it is of significant interest that 22% of older ill travelers in our cohort were over 70 years of age. This suggests that the elderly might represent an important proportion of individuals seeking information on travel-related diseases and that targeted pre-travel advice based on reliable data should be provided. We observed that older ill travelers returning to GeoSentinel sites conducted short-term, pre-arranged, and organized tourism trips more frequently, traveled more frequently to Europe and the United States, and consequently sought pre-travel advice less frequently than their younger counterparts.

For example ‘A pharmacist would definitely have to let me know if someone

was using large amounts of Ventolin without a preventer. . . .’ (GP 1), ‘. . . the pharmacist’s role would be to . . . keep the doctor and the patient up to date on. . . .’ (GP 2). In contrast, for pharmacists, accessibility, style and nature of communication was a priority. For example ‘The ideal GP would be . . . a good communicator and accessible.’ ACP-196 manufacturer (pharmacist 3), ‘. . . willing to view us as an equal partner.’ (pharmacist 10), ‘. . . smart and care[ing] . . .’ (pharmacist 4), ‘. . . approachable, and available to speak with (me) . . .’ (pharmacist 8). GPs and pharmacists were also mismatched in their perceptions of asthma management. GPs felt that asthma was well managed in the community, that asthma care had improved significantly in the last decade and that although there may be room for improvement, acute/problematic asthma was rarely seen in GP surgeries. In contrast, pharmacists perceived asthma control to be variable, ranging from poor to good. Pharmacists recognised that some patients were readily identifiable as having poorly controlled asthma, identifying reasons such as poor adherence, self-management (e.g.

lack of written self-management plan ownership) or reluctance to engage in care as the problem. For example ‘it seems to be better managed nowadays, maybe with the new drugs . . .’ (GP 5). In contrast to ‘. . . [management of asthma control is] overall terrible. . . . I don’t think that pharmacy has helped much.’ (pharmacist 11). With regards to why: ‘. . . a fear about steroids [medications] in the community . . .’ (pharmacist 18), ‘. . . They are either X-396 nmr very well looked after or not at all.’ (pharmacist 3), ‘. . . most of them don’t manage their asthma very well . . .’ (pharmacist 15). When it came to the needs of patients, GPs and pharmacists perceptions differed to some extent. Not all GPs were convinced that patients would benefit from receiving specialised and individualised education. Pharmacists recognised that while

some patients are resistant to advice, patient education would result in patient benefits. For example: with regards to receiving additional information, ‘. . . maybe newly diagnosed ones [patients] . . . it Dehydratase would enhance their understanding’ (GP 4), ‘benefits from education . . . definitely . . . [as] a lot become blasé . . .’ (pharmacist 10), compared with ‘. . . I don’t know whether there’s any extra benefit . . . they’re not listening’ (GP 7) and ‘. . . there is that core element who will not conform, and it doesn’t matter what you do. You can take a horse to water but you can’t make it drink.’ (pharmacist 6). With regards to who should be providing specialised support, GPs suggested that practice nurses should do this but as long as the HCP was trained, it could be the pharmacist. Pharmacists suggested all HCPs should be involved and the issue of reimbursement was raised. For example ‘. . .

In a survey of 42 sub-Saharan African countries, where the prevalence of HIV infection is high, 10–65% of women responded that their last pregnancy had

been unintended [9]. In the United States of America (USA), Koenig and colleagues found that, of 1183 births to 1090 adolescent HIV-positive girls, only 50% knew their HIV status prior to the pregnancy, 67% had been previously pregnant and 83.3% of the pregnancies were unplanned [8]. Unintended pregnancies are similarly common in the general population [10–13]. The 2002 National Survey of Family Growth showed that 49% of pregnancies to women aged 18–44 years old in 2001 in the USA were unintended [10]. The U.S. Behavioral Risk Factor Surveillance System survey data selleck antibody inhibitor showed that 29% of 18- to 44-year-old fertile women were at high risk for unintended pregnancy, based on the report of failure

to use any form of contraception [11]. A 19% pregnancy rate was observed among a cohort of women seen in a sexually transmitted disease clinic in the USA, all of whom reported ‘no intention of becoming pregnant’ at Metformin solubility dmso their previous visit [12]. The 2008 Preconception Health Survey of 200 pregnant women and 151 women with a child under the age of 7 years living in Ontario, Canada, revealed that 30% of pregnancies were unplanned and 67% of women were happy with their last pregnancy [13]. To explore rates and correlates of unintended pregnancies among adult HIV-positive women in Canada, we conducted a secondary analysis of a cross-sectional study of HIV-positive women of reproductive age living in Ontario, which collected information about Baricitinib the primary outcome of fertility intentions along with pregnancy history data and whether pregnancies were intended [14]. This analysis aimed to determine the prevalence of unintended pregnancies in an HIV-positive female population before and after their HIV diagnosis and to identify potential correlated sociodemographic and clinical variables for those unintended pregnancies after HIV diagnosis. By highlighting these results,

our aim is to make recommendations that will positively impact the behaviour of HIV-positive women and their healthcare providers, by ensuring that the discussion of pregnancy planning is a part of routine HIV care, thereby increasing the likelihood of more planned pregnancies and providing an opportunity for optimal management. This was a secondary analysis of a larger study, the details of which are reported elsewhere [14]. The main data set was from a cross-sectional study using a survey instrument which was conducted with participants who met the following inclusion criteria: (1) HIV-positive, (2) biologically female, (3) of reproductive age (between the ages of 18 and 52 years), (4) living in Ontario, Canada, and (5) able to read English or French. The upper age limit was chosen to reflect the cut-off for fertility clinic consultation in Canada.

p.m., standardized to a density equivalent of approximately 1 × 108 CFU mL−1, and diluted to a working concentration of 1 × 106 CFU mL−1. To examine the direct effect of live P. aeruginosa on A. fumigatus biofilm formation, standardized suspensions of conidia and bacterial cells were combined in equal volumes in a 96-well microtitre plate (Corning, NY) in MOPS-buffered RPMI (Sigma) and incubated overnight at 37 °C. The effect of killed bacterial cells on A. fumigatus biofilm formation was also investigated. Pseudomonas aeruginosa was

centrifuged, washed twice in RG7204 chemical structure phosphate-buffered saline (PBS) and resuspended in 100% methanol for 2 h. The dead cells were then centrifuged and washed three times in PBS to remove any remaining trace of methanol CAL-101 clinical trial and finally resuspended to 1 × 106 CFU mL−1 in RPMI. To confirm bacterial killing, aliquots of the bacterial cells were spread onto LB agar plates and incubated overnight at 37 °C. Equal volumes of standardized conidia and methanol-killed bacterial cells were combined in a 96-well microtitre plate and incubated overnight at 37 °C. Aspergillus fumigatus biofilms were also prepared, as described previously (Mowat et al., 2007), and challenged with P. aeruginosa. The resultant A. fumigatus biomass after exposure

of mature biofilms and conidia undergoing morphological differentiation, to both live and dead bacterial cells, were quantified as described previously by our group (Mowat et al., 2007). In addition, scanning electron microscopy (SEM) of A. fumigatus biofilms grown on Thermanox™ coverslips (Nalge Nunc Inc., Rochester, NY) and challenged with P. aeruginosa (PAO1) for 24 h was examined microscopically, as described previously (Mowat et al., 2007). These were viewed using a Zeiss Evo SEM in high-vacuum mode

at 10 kV. A standardized overnight culture of all bacterial strains was centrifuged for 5 min at 3000 g to pellet the cells. The harvested supernatant was then filter sterilized through a 0.22-μM filter (Millipore UK Limited). An aliquot of the supernatant was also heat treated at 80 °C for 10 min. The supernatants were then combined (9 : 1) with 10 × concentrated MOPS-buffered Farnesyltransferase RPMI containing 1 × 105 conidia mL−1, aliquoted into a 96-well microtitre plate and incubated overnight at 37 °C. To assess the role of an indirect interaction between A. fumigatus and P. aeruginosa, a 12 mm Transwell® (Corning, NY) permeable support system was utilized. The Transwell® system enables the coculturing of the two pathogens in two separate compartments connected via a microporous membrane (0.4 μm). Aspergillus fumigatus conidia were inoculated into the lower compartment and P. aeruginosa were inoculated into the upper chamber of the insert, which was then incubated overnight at 37 °C. The following P. aeruginosa strains were tested using the Transwell® system: PAO1, PAO1:ΔLasI and PAO1:ΔLasR. Wells containing only A. fumigatus or P. aeruginosa were included as controls.

Free heme, with a molecular weight of around 616 Da, passes through this filter, whereas each hemoglobin subunit, with a molecular weight of approximately 17 kDa, is retained. The growth of ΔhemB in TSB supplemented with either the < 10-kDa hemoglobin fraction or the > 10-kDa hemoglobin fraction was measured after 8 h. Only the > 10-kDa fraction was able to relieve the heme auxotrophy of ΔhemB (Fig. 2b), demonstrating that negligible levels of free heme were present in the hemoglobin preparation. The lipoprotein component of the membrane-localized INCB018424 ABC transporter of the Isd system is encoded by isdE. With the aim of investigating

heme transport in the SCV ΔhemB strain, markerless deletions of the isdE gene were made

in the LS-1 and ΔhemB strains. Deletion of isdE produced no detectable alteration of growth in TSB in either the LS-1 (data not shown) or ΔhemB background (Fig. 3a). When the ΔhemBΔisdE LDE225 mw strain was grown in TSB in the presence of 1.5 μM hemin, the growth defect caused by the hemB mutation was abolished (Fig. 3b), demonstrating that S. aureus is able to internalize exogenous heme in the absence of the isdE gene. The htsA gene encodes the lipoprotein component of the proposed heme transport system Hts. The role of Hts in the transport of the siderophore, staphyloferrin A, has been demonstrated (Beasley et al., 2009; Grigg et al., 2010). However, it has been suggested that the Hts transporter may have broader specificity enabling transport of multiple substrates, including heme

(Hammer & Skaar, 2011). To help address this question, markerless deletions of htsA were made in S. aureus LS-1 and ΔhemB. The htsA mutation caused no change in the growth of either the LS-1 (data not shown) or ΔhemB backgrounds (Fig. 3a). When the ΔhemBΔhtsA strain was grown in TSB supplemented with 1.5 μM hemin, the growth deficiency caused by the disruption of the heme biosynthesis pathway was restored (Fig. 3b), demonstrating that htsA is not required for acquisition of heme by S. aureus. The ΔisdE and ΔhtsA mutations were then incorporated BCKDHA together into the same strains in both LS-1 and ΔhemB backgrounds to examine the possibility that IsdE and HtsA may be functionally redundant. The combined htsA and isdE mutations did not result in any alteration of growth in TSB in either LS-1 (data not shown) or ΔhemB (Fig. 3a). Growth of the ΔhemBΔisdEΔhtsA triple-deletion strain in TSB with 1.5 μM hemin again showed that hemin was able to restore the growth defect caused by the hemB deletion (Fig. 3b). These data demonstrate that both htsA and isdE, alone or in combination, are dispensable for the acquisition of external heme by S. aureus. IsdB and IsdH contribute to the binding of hemoglobin to the S.