The plasma membrane glycoprotein receptor CD163 is a member of the scavenger receptor cystein-rich (SRCR) superfamily class B that is highly expressed on resident tissue macrophages in vivo. Previously, the molecule has been shown to act as a receptor for hemoglobinhaptoglobin complexes and to mediate cell-cell interactions between macrophages and developing erythroblasts in erythroblastic islands. Here, we provide evidence for a potential role for CD163 in host defense. In particular, we demonstrate that CD163 can function as a macrophage receptor for bacteria. CD163 was shown to bind both Gram-positive and -negative bacteria, and a previously identified cell-binding motif in the second scavenger domain of CD163 was sufficient to mediate this binding. Expression of CD163 in monocytic cells promoted bacteria-induced proinflammatory cytokine production. Finally, newly generated antagonistic antibodies against CD163 were able to potently inhibit cytokine production elicited by bacteria in freshly isolated human monocytes. These findings identify CD163 as a macrophage receptor for bacteria and suggest that, during bacterial infection, CD163 on resident tissue macrophages acts as an innate immune sensor and inducer of local inflammation. (Blood. 2009;113:887-892)

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The oral cavity is colonized by microorganisms growing in biofilms in which interspecies interactions take place. Streptococcus mutans grows in biofilms on enamel surfaces and is considered one of the main etiological agents of human dental caries. Candida albicans is also commonly found in the human oral cavity, where it interacts with S. mutans. C. albicans is a polymorphic fungus, and the yeast-to-hypha transition is involved in virulence and biofilm formation. The aim of this study was to investigate interkingdom communication between C. albicans and S. mutans based on the production of secreted molecules. S. mutans UA159 inhibited C. albicans germ tube (GT) formation in cocultures even when physically separated from C. albicans. Only S. mutans spent medium collected in the early exponential phase (4-h-old cultures) inhibited the GT formation of C. albicans. During this phase, S. mutans UA159 produces a quorum-sensing molecule, competence-stimulating peptide (CSP). The role of CSP in inhibiting GT formation was confirmed by using synthetic CSP and a comC deletion strain of S. mutans UA159, which lacks the ability to produce CSP. Other S. mutans strains and other Streptococcus spp. also inhibited GT formation but to different extents, possibly reflecting differences in CSP amino acid sequences among Streptococcus spp. or differences in CSP accumulation in the media. In conclusion, CSP, an S. mutans quorum-sensing molecule secreted during the early stages of growth, inhibits the C. albicans morphological switch.The oral cavity is colonized by many different microbial species, where most reside in biofilms. Because of its multispecies nature, the oral microbial community is one of the best biofilm models for studying interspecies interactions (17). The gram-positive bacterium Streptococcus mutans shows a high prevalence in dental biofilms, and it is considered to be the major etiological agent involved in human dental caries (21). The fungal species Candida albicans constitutes a minor part of the total microbial flora (19) and can be isolated as a commensal from the oral cavity of 50% to 60% of healthy adults (33). However, in immunocompromised individuals (for example, due to human immunodeficiency virus infection or as a result of chemotherapy) and elderly patients, this fungus often leads to candidiasis (24). C. albicans is a polymorphic fungus that can exist in three morphotypes: budding yeast, pseudohypha, and true hypha (5). The morphological switch from yeast to hyphal cells is important in many processes, such as virulence (22) and biofilm formation (10, 18), and is therefore the subject of many studies.Bacteria and yeasts are often found together in vivo, and there is growing evidence that interspecies, and even interkingdom, interactions occur within these populations (7). These interactions can be mediated through signaling molecules (40), as recently described for the interaction between C. albicans and Pseudomonas aeruginosa, an opportunistic bacterial pathogen (15). N-3-oxo-C 12 homoserine lacton...

Five new hydroanthraquinone derivatives, tetrahydroaltersolanols C-F (1-4) and dihydroaltersolanol A (5), and five new alterporriol-type anthranoid dimers, alterporriols N-R (12-16), along with seven known analogues (6-11 and 17), were isolated from the culture broth and the mycelia of Alternaria sp. ZJ-2008003, a fungus obtained from a Sarcophyton sp. soft coral collected from the South China Sea. Their structures and the relative configurations were elucidated using comprehensive spectroscopic methods including 1D and 2D NOE spectra as well as single-crystal X-ray crystallography. Compound 13 represents the first isolated alterporriol dimer with a C-4-C-4' linkage, and the absolute configuration of 4 was determined using the modified Mosher's method. Compounds 1 and 15 exhibited antiviral activity against the porcine reproductive and respiratory syndrome virus (PRRSV), with IC₅₀ values of 65 and 39 μM, respectively. Compound 14 showed cytotoxic activity against PC-3 and HCT-116 cell lines, with IC₅₀ values of 6.4 and 8.6 μM, respectively.

For decades, fluoride has been used extensively as an anti-caries agent. It not only protects dental hard tissue, but also inhibits bacterial growth and metabolism. The antimicrobial action of fluoride is shown in three main aspects: the acidogenicity, acidurance, and adherence to the tooth surface. To counteract the toxic effect of fluoride, oral bacteria are able to develop resistance to fluoride through either phenotypic adaptation or genotypic changes. Strains that acquire fluoride resistance through the latter route show stable resistance and can usually resist much higher fluoride levels than the corresponding wild-type strain. This review summarizes the characteristics of fluoride-resistant strains and explores the mechanisms of fluoride resistance, in particular the recent discovery of the fluoride exporters. Since the fluoride resistance of the cariogenic bacterium Streptococcus mutans has been studied most extensively, this review mainly discusses the findings related to this species.

BackgroundPeriodontitis is a bacterial infection of the periodontal tissues. The Gram-negative anaerobic bacterium Porphyromonas gingivalis is considered a major causative agent. One of the virulence factors of P. gingivalis is capsular polysaccharide (CPS). Non-encapsulated strains have been shown to be less virulent in mouse models than encapsulated strains.ResultsTo examine the role of the CPS in host-pathogen interactions we constructed an insertional isogenic P. gingivalis knockout in the epimerase-coding gene epsC that is located at the end of the CPS biosynthesis locus. This mutant was subsequently shown to be non-encapsulated. K1 capsule biosynthesis could be restored by in trans expression of an intact epsC gene. We used the epsC mutant, the W83 wild type strain and the complemented mutant to challenge human gingival fibroblasts to examine the immune response by quantification of IL-1β, IL-6 and IL-8 transcription levels. For each of the cytokines significantly higher expression levels were found when fibroblasts were challenged with the epsC mutant compared to those challenged with the W83 wild type, ranging from two times higher for IL-1β to five times higher for IL-8.ConclusionsThese experiments provide the first evidence that P. gingivalis CPS acts as an interface between the pathogen and the host that may reduce the host's pro-inflammatory immune response. The higher virulence of encapsulated strains may be caused by this phenomenon which enables the bacteria to evade the immune system.

It is known that fluoride-resistant microorganisms are different from fluoride-sensitive ones in growth, adherence and metabolic activity. It was hypothesized that these phenotypic differences were due to stable genotypic changes in the fluoride-resistant strains. However, until now, no studies have reported these genotypic changes. The aim of this study is to identify such changes in a fluoride-resistant Streptococcus mutans strain (C180-2FR) using whole-genome shotgun (WGS) sequencing and to examine the potential function of the identified mutations by comparing gene expression between the fluoride-sensitive (C180-2) and C180-2FR strains. We performed 50 bp paired-end Illumina shotgun sequencing for both strains. Through extensive bioinformatic analysis, we were able to identify 8 single nucleotide polymorphisms (SNPs) in the genome of C180-2FR, which were further confirmed by Sanger sequencing. Expression of the genes containing or in proximity to the SNPs in C180-2 and C180-2FR was then quantified by real-time PCR. A gene cluster containing genes coding for fluoride antiporters was up-regulated 10-fold in C180-2FR when compared to that in C180-2, independent of growth phase. Two SNPs are located in this gene cluster, one in its promoter region and the other in its protein-coding region. In addition, one gene, which codes for a putative glycerol uptake facilitator protein, was found to be down-regulated by 60% in C180-2FR at an early growth phase. The promoter region of this gene contained a SNP. No difference in expression was found for the other SNP-containing genes. In summary, using WGS sequencing, we were able to uncover genetic changes in the genome of a fluoride-resistant strain. These findings can provide new insights into the mechanism of microbial fluoride resistance.

To develop a bacterial demineralization model, we grew Streptococcus mutans biofilms in a constant depth film fermentor (CDFF) and studied the effects of sucrose pulsing frequency (SPF) in time on dentin demineralization. S. mutans biofilms were grown in dentin specimens with grooves and on dentin surface specimens for 20 days. During the experiments, 2% sucrose was pulsed either 4 or 8 times per day for periods of 30 min. Diluted brain-heart infusion medium containing 25 mM PIPES buffer and 1.5 mM CaCl₂ was pulsed as the alternative growth medium. Specimens with intact biofilms were taken out on days 5, 12 and 20. The model was assessed by viable counts of the biofilm, mineral loss and lesion depth in the dentin specimens (by transversal microradiography) and pH measurements in the groove (by pH microelectrode). The results showed that biofilms formed on the dentin surface specimens were constant in viable counts for the low SPF, while this parameter tended to increase with time under the high SPF. Lesions with intact surfaces were formed and the lesion size increased significantly over time and increased significantly with increasing SPF. Typical Stephan curves were found after sucrose pulsing. The pH inside the groove returned to neutral under low SPF, but remained below 6.5 under high SPF. With the CDFF S. mutans biofilm model, lesions can be created in dentin within reasonable experimental time periods, as a result of the presence of a biofilm and in response to carbohydrate challenges.