Free thyroxine, brain frailty and clock drawing test performance in patients with acute minor stroke or transient ischaemic attack.

OBJECTIVE: Thyroid dysfunction is associated with an elevated risk of cognitive decline, but the mechanism underlying this relationship is elusive. In this study, we investigate the relationships between free thyroxine (FT4), brain frailty and clock drawing test (CDT) performance in patients with acute minor stroke or transient ischaemic attack (TIA). DESIGN, PATIENTS AND MEASUREMENTS: A total of 204 consecutive patients admitted to our hospital within 72 h after the onset of acute minor stroke or TIA were prospectively enroled and categorized in terms of quartiles of FT4 between March 2018 and August 2019. Brain frailty on magnetic resonance imaging was rated according to previously published criteria. Cognitive performance was assessed with the CDT. RESULTS: Generalized linear analysis revealed that FT4 was independently associated with higher brain frailty score after adjusting potential confounders (ß, 0.03; 95% confidence interval [CI], 0.00-0.06; p = 0.0205), which is consistent with the result of FT4 (quartile) as a categorical variable (ß, 0.34; 95% CI, 0.01-0.68; p = 0.0059; ptrend = 0.0807). A nonlinear relationship was detected between FT4 and brain frailty score, which had an inflection point of 1.19. FT4 was also associated with poor CDT performance (odds ratio, 1.15; 95% CI, 1.04-1.26; p = 0.0051). And mediation analysis found that brain frailty partially mediated the positive relationship between FT4 and poor CDT performance (indirect effect = 0.0024; 95% CI, 0.0003-0.01, p = 0.04). CONCLUSIONS: Our findings suggested that a higher FT4 level was associated with a higher brain frailty score and poorer CDT performance, and brain frailty might play an important effect on the association between FT4 and cognitive decline.

Dysbiosis of nail microbiome in patients with psoriasis.

Shifts in skin microbiome are considered to be involved in the pathogenesis of psoriasis. However, data on the microbial dysbiosis of nail psoriasis are scarce. In this study, we aim to investigate and characterize the nail bacterial and fungal microbiome in patients with psoriasis. Nail samples were collected prospectively from 36 subjects with nail psoriasis, 24 psoriatic subjects without nail involvement and 32 healthy controls. Amplicon sequencing was performed to evaluate the bacterial and fungal community compositions. Significant alterations in the bacterial microbiome were found in the nail samples of psoriatic patients. The unaffected nails in psoriatic patients were associated with higher bacterial diversity, and a higher relative abundance of Enhydrobacter, whereas nail psoriasis was correlated with a decreased relative abundance of Anaerococcus. Shifts in fungal community composition were reflected by a higher proportion of Malassezia in the unaffected nails of psoriatic patients and an increased proportion of Candida in psoriatic nails. Shifts in the nail microbiome in psoriasis suggest a potential role of microbes in the development of nail psoriasis. Future researches focusing on these microorganisms may help to explain the pathogenesis of psoriasis.

Bathiapeptides: Polythiazole-Containing Peptides from a Marine Biofilm-Derived Bacillus sp.

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 µM. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.

Ketoconazole 2% cream alters the skin fungal microbiome in seborrhoeic dermatitis: a cohort study.

BACKGROUND: Seborrhoeic dermatitis (SD) is a common chronic inflammatory dermatosis. Current theories on the pathogenesis of SD highlight the role of microbes on the skin surface. Ketoconazole is commonly used for the treatment of SD; however, there are limited data focusing on the effects of ketoconazole in shaping the skin microbiome in patients with SD. AIM: In this prospective cohort study, we used a high-throughput DNA sequencing method to characterize the cutaneous microbial communities of patients with SD before and after topical ketoconazole treatment. METHODS: In total, 30 patients with facial SD and 15 age- and sex-matched healthy controls (HCs) were enrolled in this study. Skin swabs were collected from SD lesional sites of the cheek at baseline, after ketoconazole treatment and 2 weeks post-treatment. DNA was extracted from skin samples. The bacterial 16S V3V4 rRNA and fungal internal transcribed spacer 1-5F regions were sequenced, and the microbial community compositions were analysed. RESULTS: Significantly lower bacterial and fungal diversities were detected at the lesional sites of facial SD compared with HCs. A decreased relative abundance of Cutibacterium and increased abundances of Malassezia and Staphylococcus were found in facial SD. Disease diversity was positively correlated with the relative abundances of Malassezia, Staphylococcus and Corynebacterium, while transepidermal water loss was negatively associated with the relative abundance of Cutibacterium. After ketoconazole treatment, fungal Shannon diversity and the relative abundances of Candida and Aspergillus were significantly increased at the lesional sites, and the relative abundance of Malassezia showed a decreasing trend. These changing trends were maintained until 2 weeks post-treatment. CONCLUSION: Facial SD showed lower fungal diversity accompanied by increased relative abundances of Malassezia and Staphylococcus and decreased relative abundance of Cutibacterium. Ketoconazole treatment reduced Malassezia and increased fungal diversity to restore skin microbial communities.

Dysbiosis of skin mycobiome in atopic dermatitis.

Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease with an increasing prevalence worldwide. The aetiology and pathogenesis of AD have not been fully elucidated. Previous studies have suggested the role of fungi as a triggering factor in the development AD. Here we conducted a systematic review to investigate the skin mycobiome profiles in AD and to address whether there is an association between fungal dysbiosis and AD. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between January 1st, 2010 and April 21st, 2021. A total of 11 human studies and 3 animal studies were included in this analysis. Fungal dysbiosis was observed in AD lesions with a depleted amount of Malassezia and a higher abundance of filamentous fungi. A positive correlation between Candida and Staphylococcus was also demonstrated in AD. We supposed that specific species of Malassezia spp. and Candida spp. may play a role in the pathogenesis of AD by interacting with the pathogenic bacteria. Topical application of emollients could improve the skin barrier function and restore the skin fungal flora by increasing the amount of Malassezia. Further studies focusing on the complex interplay between specific skin fungi and the host can provide better insight into the role of microorganisms in the pathogenesis of AD.

Characterisation of the nail microbiome in psoriatic and nonpsoriatic patients with onychomycosis.

BACKGROUND: Onychomycosis (OM) is the most common infectious nail disease, and it occurs frequently in patients with psoriasis. Microbial community shifts have been suggested to play a role in psoriasis and fungal infection occurrence. OBJECTIVES: To investigate and compare nail microbial community compositions in psoriatic and nonpsoriatic patients with OM. METHODS: Toenail samples were collected from nonpsoriatic patients with OM, psoriatic patients with nail psoriasis (NP) and OM, patients with only NP and healthy controls. Bacterial and fungal community compositions were analysed by amplicon sequencing of the V3-V4 regions of the 16S rDNA gene and the ITS1 region, respectively. RESULTS: Psoriatic OM patients had higher bacterial and fungal alpha diversities. Taxonomic analysis revealed a significantly lower relative abundance of Trichophyton rubrum (32.88% vs 82.18%, p < .001) and an increased trend of the abundance of Candida in psoriatic patients with OM than in nonpsoriatic patients. Nonpsoriatic patients with OM had a higher abundance of Staphylococcus than healthy controls (59.66% vs 45.76%, p < .05). Trichophyton, Alternaria and Malassezia could accurately differentiate psoriatic and nonpsoriatic patients with OM, with an area under the curve (AUC) of 0.86. The severity of OM was positively correlated with the relative abundance of Trichophyton rubrum. Further, Trichophyton was positively correlated with Staphylococcus and negatively correlated with Corynebacterium, Anaerococcus, Malassezia and Alternaria. CONCLUSIONS: The nail microbiome in psoriatic patients with OM has distinct bacterial and fungal signatures, suggesting that different dysbiosis is associated with the pathogenesis of OM in psoriatic and nonpsoriatic patients.

Altered skin fungal and bacterial community compositions in tinea capitis.

BACKGROUND: Tinea capitis is an infection of the scalp and hair shaft caused by dermatophytes that predominantly occurs in children. Skin fungal infections have been found to be associated with alterations in the overall bacterial and fungal communities. However, the scalp microbiome in tinea capitis have not been fully investigated. OBJECTIVES: To investigate and compare the scalp bacterial and fungal microbiomes between children with tinea capitis and healthy children and between children and adults. METHODS: Skin samples were collected from the scalp. Bacterial and fungal community compositions were analysed by amplification sequencing of the V3-V4 of 16S rDNA and ITS1-5F, respectively. RESULTS: The predominant fungi detected using amplicon sequencing were consistent with the culture- or real-time PCR-positive pathogens in most samples. Children with tinea capitis had lower fungal and higher bacterial Shannon diversity than healthy children. A higher relative abundance of pathogenic fungi and significant alterations in the bacterial community in the lesional sites of tinea capitis than healthy scalps. Compared with adults, healthy children were characterised by higher Shannon diversities with significantly lower relative abundances of Malassezia and Cutibacterium and higher relative abundances of Candida and Streptococcus. CONCLUSIONS: We demonstrated that tinea capitis was characterised by significant alterations in both fungal and bacterial communities and amplicon sequencing could be a complementary method for pathogen identification.

Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the DNA-damage response and leads to cell death.

Of the ~80 putative toxin-antitoxin (TA) modules encoded by the bacterial pathogen Mycobacterium tuberculosis (Mtb), three contain antitoxins essential for bacterial viability. One of these, Rv0060 (DNA ADP-ribosyl glycohydrolase, DarGMtb ), functions along with its cognate toxin Rv0059 (DNA ADP-ribosyl transferase, DarTMtb ), to mediate reversible DNA ADP-ribosylation (Jankevicius et al., 2016). We demonstrate that DarTMtb -DarGMtb form a functional TA pair and essentiality of darGMtb is dependent on the presence of darTMtb , but simultaneous deletion of both darTMtb -darGMtb does not alter viability of Mtb in vitro or in mice. The antitoxin, DarGMtb , forms a cytosolic complex with DNA-repair proteins that assembles independently of either DarTMtb or interaction with DNA. Depletion of DarGMtb alone is bactericidal, a phenotype that is rescued by expression of an orthologous antitoxin, DarGTaq , from Thermus aquaticus. Partial depletion of DarGMtb triggers a DNA-damage response and sensitizes Mtb to drugs targeting DNA metabolism and respiration. Induction of the DNA-damage response is essential for Mtb to survive partial DarGMtb -depletion and leads to a hypermutable phenotype.

Realization of Supersymmetry and Its Spontaneous Breaking in Quantum Hall Edges.

Supersymmetry (SUSY) relating bosons and fermions plays an important role in unifying different fundamental interactions in particle physics. Since no superpartners of elementary particles have been observed, SUSY, if present, must be broken at low-energy. This makes it important to understand how SUSY is realized and broken, and study their consequences. We show that an N=(1,0) SUSY, arguably the simplest type, can be realized at the edge of the Moore-Read quantum Hall state. Depending on the absence or presence of edge reconstruction, both SUSY-preserving and SUSY broken phases can be realized in the same system, allowing for their unified description. The significance of the gapless fermionic Goldstino mode in the SUSY broken phase is discussed.

Skin microbiome alterations in seborrheic dermatitis and dandruff: A systematic review.

Seborrheic dermatitis (SD) and dandruff (DF) are common chronic inflammatory skin diseases characterized by recurrent greasy scales, sometimes with erythema and itchiness. Although the exact pathophysiology of the disease is still unclear, current theories highlight the role of microbes on the skin surface in the pathogenesis of SD. Here, we conducted a systematic review to investigate the skin microbiome alterations in patients with SD/DF. We searched Medline/PubMed, Embase and Web of Science for research studies published in English between 1 January 2000 and 31 December 2020. A total of 12 studies with 706 SD/DF samples and 379 healthy samples were included in this study. The scalp and face were predominated by the fungi of Ascomycota and Basidiomycota and the bacteria of Actinobacteria and Firmicutes. In general, the included studies demonstrated an increased Malassezia restricta/Malassezia globosa ratio and a reduction in the Cutibaterium/Staphylococcus ratio in the setting of SD/DF. Staphylococcus was associated with epidermal barrier damage, including elevated levels of trans-epidermal water loss and pH, while Cutibacterium had a positive correlation with water content. Malassezia was also found to be related to an increased itching score and disease severity. Further studies focusing on the interactions between various microbes and the host and microbes can help us to better understand the pathogenesis of SD/DF.

Invasive dermatophyte infection: A systematic review.

Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis.

Discovery of Antibiofilm Activity of Elasnin against Marine Biofilms and Its Application in the Marine Antifouling Coatings.

Biofilms are surface-attached multicellular communities that play critical roles in inducing biofouling and biocorrosion in the marine environment. Given the serious economic losses and problems caused by biofouling and biocorrosion, effective biofilm control strategies are highly sought after. In a screening program of antibiofilm compounds against marine biofilms, we discovered the potent biofilm inhibitory activity of elasnin. Elasnin effectively inhibited the biofilm formation of seven strains of bacteria isolated from marine biofilms. With high productivity, elasnin-based coatings were prepared in an easy and cost-effective way, which exhibited great performance in inhibiting the formation of multi-species biofilms and the attachment of large biofouling organisms in the marine environment. The 16S amplicon analysis and anti-larvae assay revealed that elasnin could prevent biofouling by the indirect impact of changed microbial composition of biofilms and direct inhibitory effect on larval settlement with low toxic effects. These findings indicated the potential application of elasnin in biofilm and biofouling control in the marine environment.

Natural polyphenol assisted delivery of single-strand oligonucleotides by cationic polymers.

Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polyphenol to facilitate the condensation of single-strand oligonucleotides by cationic polymers. Green tea catechin complexed with single-strand oligonucleotides to form anionic nanoparticles, which were further coated by low molecular weight cationic polymers to increase their cell internalization. The resulting core-shell structured nanoparticles, so-called green nanoparticles (GNPs), showed improved cargo stability, and achieved high efficiency in the delivery of several types of single-strand oligonucleotides including antisense oligonucleotides, anti-miRNA, and DNAzyme. This study provides a facile strategy for the efficient delivery of single-strand oligonucleotides.

Metagenomic Analysis of Zinc Surface-Associated Marine Biofilms.

Biofilms are a significant source of marine biofouling. Marine biofilm communities are established when microorganisms adhere to immersed surfaces. Despite the microbe-inhibiting effect of zinc surfaces, microbes can still attach to the surface and form biofilms. However, the diversity of biofilm-forming microbes that can attach to zinc surfaces and their common functional features remain elusive. Here, by analyzing 9,000,000 16S rRNA gene amplicon sequences and 270 Gb of metagenomic data, we comprehensively explored the taxa and functions related to biofilm formation in subtidal zones of the Red Sea. A clear difference was observed between the biofilm and adjacent seawater microbial communities in terms of the taxonomic structure at phylum and genus levels, and a huge number of genera were only present in the biofilms. Saturated alpha-diversity curves suggested the existence of more than 14,000 operational taxonomic units in one biofilm sample, which is much higher than previous estimates. Remarkably, the biofilms contained abundant and diverse transposase genes, which were localized along microbial chromosomal segments and co-existed with genes related to metal ion transport and resistance. Genomic analyses of two cyanobacterial strains that were abundant in the biofilms revealed a variety of metal ion transporters and transposases. Our analyses revealed the high diversity of biofilm-forming microbes that can attach to zinc surfaces and the ubiquitous role of transposase genes in microbial adaptation to toxic metal surfaces.

Rapid remission of Stevens-Johnson syndrome by combination therapy using etanercept and intravenous immunoglobulin and a review of the literature.

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are spectrum of rare, acute, and life-threatening delayed-type drug hypersensitivity reactions that are associated with high mortality rates. However, no therapeutic standard has been proposed for SJS/TEN. Here, we report a case of a patient diagnosed with Stevens-Johnson syndrome whose disease progression was halted by a single dose of etanercept and was treated successfully. In addition, we reviewed the literature reporting patients with SJS/TEN treated with similar regimens.

Distribution, diversity and functional dissociation of the mac genes in marine biofilms.

Bacteria produce metamorphosis-associated contractile (MAC) structures to induce larval metamorphosis in Hydroides elegans. The distribution and diversity of mac gene homologs in marine environments are largely unexplored. In the present study mac genes were examined in marine environments by analyzing 101 biofilm and 91 seawater metagenomes. There were more mac genes in biofilms than in seawater, and substratum type, location, or sampling time did not affect the mac genes in biofilms. The mac gene clusters were highly diverse and often incomplete while the three MAC components co-occurred with other genes of different functions. Genomic analysis of four Pseudoalteromonas and two Streptomyces strains revealed the mac genes transfers among different microbial taxa. It is proposed that mac genes are more specific to biofilms; gene transfer among different microbial taxa has led to highly diverse mac gene clusters; and in most cases, the three MAC components function individually rather than forming a complex.

Mycetoma in China: A Case Report and Review of the Literature.

Mycetoma is a chronic granulomatous infectious disease that can affect the skin, subcutaneous tissue, fascia and bone. It can be caused by filamentous bacteria or fungi and usually involves the legs and feet. Mycetoma is endemic in tropical and subtropical regions and is easily misdiagnosed in clinical practice because of its nonspecific clinical features and lack of awareness of the disease. Although mycetoma is very rare in mainland China, an increasing number of cases have been reported in recent years. Here, we report a case of mycetoma in a patient who was misdiagnosed many years before receiving the correct treatment, leading to disease progression and motion limitation. The grains that represent microorganismal colonies were important clues for diagnosis. We also reviewed reported cases of mycetoma in mainland China. The majority of cases were reported from southern regions. Actinomycetoma was more commonly reported than was eumycetoma. The causative agents of actinomycetoma included Nocardia brasiliensis, N. asteroides, N. otitidiscaviarum, N. ninae and Gordonia terrae, and the causative fungi of eumycetoma were identified as Madurella mycetomatis, Fonsecaea pedrosoi and Acremonium falciforme. Notably, the diagnosis of mycetoma was delayed from months to decades in all of the patients, likely due to a lack of clinical experience. Our literature review suggests the importance of increased awareness of mycetoma in clinical practice, especially in non-endemic regions. Further investigative studies are needed to determine the real incidence of the disease in China.

Baseline Neutrophil Counts and Neutrophil Ratio May Predict a Poor Clinical Outcome in Minor Stroke Patients with intravenous Thrombolysis.

BACKGROUND: Evidence about whether neutrophil counts, neutrophil ratio linked with clinical outcome in patients with minor stroke after thrombolysis is scarce. The purpose of this study is to explore the association of neutrophil counts, neutrophil ratio with the 90-day clinical outcome in patients with minor stroke treated with intravenous thrombolysis. MATERIALS AND METHODS: A total of 163 patients with minor stroke treated with thrombolysis within window time were recruited from 2013 to 2017. Their total neutrophil and leukocyte counts on admission were measured. Disability or death (defined as a modified Rankin scale score ≥2) at 90-day were captured. Multiple logistic regression models were used to estimate the association between neutrophil counts, and neutrophil ratio to clinical outcome. Receiver operating characteristic curves were used to evaluate the predictive value of neutrophil counts or neutrophil ratio. RESULTS: At the 90-day follow-up, 36 patients (21%) had disability or death after stroke onset. Compared to the first tertile, the higher neutrophil counts increased the risk of 90-day disability or death (adjusted odds ratio [aOR] for third tertile: 2.93 (1.08-7.96); P for trend = .03). Similarly, higher neutrophil ratio also increased the risk of disability or death (aOR for third tertile: 5.81 (1.7-19.88); P for trend = .005). The comparison of area under the curve for neutrophil ratio versus neutrophils was .1 (P = .04). Thus, neutrophil ratio with the cutoff point of .74 had a better discriminative ability to the outcome (6.11, 2.36-15.86). CONCLUSIONS: Baseline higher neutrophil counts and neutrophil ratio were associated with an increased risk of 90-day disability or death in patients with minor stroke who received thrombolytic therapy.

Mycobacterium tuberculosis Thioredoxin Reductase Is Essential for Thiol Redox Homeostasis but Plays a Minor Role in Antioxidant Defense.

Mycobacterium tuberculosis (Mtb) must cope with exogenous oxidative stress imposed by the host. Unlike other antioxidant enzymes, Mtb's thioredoxin reductase TrxB2 has been predicted to be essential not only to fight host defenses but also for in vitro growth. However, the specific physiological role of TrxB2 and its importance for Mtb pathogenesis remain undefined. Here we show that genetic inactivation of thioredoxin reductase perturbed several growth-essential processes, including sulfur and DNA metabolism and rapidly killed and lysed Mtb. Death was due to cidal thiol-specific oxidizing stress and prevented by a disulfide reductant. In contrast, thioredoxin reductase deficiency did not significantly increase susceptibility to oxidative and nitrosative stress. In vivo targeting TrxB2 eradicated Mtb during both acute and chronic phases of mouse infection. Deliberately leaky knockdown mutants identified the specificity of TrxB2 inhibitors and showed that partial inactivation of TrxB2 increased Mtb's susceptibility to rifampicin. These studies reveal TrxB2 as essential thiol-reducing enzyme in Mtb in vitro and during infection, establish the value of targeting TrxB2, and provide tools to accelerate the development of TrxB2 inhibitors.

Chemical Genetic Interaction Profiling Reveals Determinants of Intrinsic Antibiotic Resistance in Mycobacterium tuberculosis.

Chemotherapy for tuberculosis (TB) is lengthy and could benefit from synergistic adjuvant therapeutics that enhance current and novel drug regimens. To identify genetic determinants of intrinsic antibiotic susceptibility in Mycobacterium tuberculosis, we applied a chemical genetic interaction (CGI) profiling approach. We screened a saturated transposon mutant library and identified mutants that exhibit altered fitness in the presence of partially inhibitory concentrations of rifampin, ethambutol, isoniazid, vancomycin, and meropenem, antibiotics with diverse mechanisms of action. This screen identified the M. tuberculosis cell envelope to be a major determinant of antibiotic susceptibility but did not yield mutants whose increase in susceptibility was due to transposon insertions in genes encoding efflux pumps. Intrinsic antibiotic resistance determinants affecting resistance to multiple antibiotics included the peptidoglycan-arabinogalactan ligase Lcp1, the mycolic acid synthase MmaA4, the protein translocase SecA2, the mannosyltransferase PimE, the cell envelope-associated protease CaeA/Hip1, and FecB, a putative iron dicitrate-binding protein. Characterization of a deletion mutant confirmed FecB to be involved in the intrinsic resistance to every antibiotic analyzed. In contrast to its predicted function, FecB was dispensable for growth in low-iron medium and instead functioned as a critical mediator of envelope integrity.