Frontiers in cellular and infection microbiology
-
Front Cell Infect Microbiol · Jan 2018
Transcriptome Analysis of Pseudomonas aeruginosa Cultured in Human Burn Wound Exudates.
Pseudomonas aeruginosa is a severe opportunistic pathogen and is one of the major causes of hard to treat burn wound infections. Herein we have used an RNA-seq transcriptomic approach to study the behavior of P. aeruginosa PAO1 growing directly on human burn wound exudate. A chemical analysis of compounds used by this bacterium, coupled with kinetics expression of central genes has allowed us to obtain a global view of P. aeruginosa physiological and metabolic changes occurring while growing on human burn wound exudate. ⋯ The quorum sensing systems, known to be important for the virulence of P. aeruginosa, although moderately induced, were activated even at low cell density. Analysis of bacterial metabolism emphasized importance of lactate, lipid and collagen degradation pathways. Overall, this work allowed to designate, for the first time, a global view of P. aeruginosa characteristics while growing in human burn wound exudate and highlight the possible therapeutic approaches to combat P. aeruginosa burn wound infections.
-
Front Cell Infect Microbiol · Jan 2018
Mycobacterium tuberculosis Virulent Factor ESAT-6 Drives Macrophage Differentiation Toward the Pro-inflammatory M1 Phenotype and Subsequently Switches It to the Anti-inflammatory M2 Phenotype.
Tuberculosis, a human infectious disease caused by Mycobacterium tuberculosis (M.tb), is still a major cause of morbidity and mortality worldwide. The success of M.tb as a pathogen relies mainly on its ability to divert the host innate immune responses. One way by which M.tb maintains a persistent infection in a "silent" granuloma is to inhibit inflammation and induce an immunoregulatory phenotype in host macrophages (MΦs). ⋯ Moreover, gene expression profiling of these cells showed that ESAT-6 induced downregulation of M1 MΦ cell surface molecules CD80 and CD86, transcription factors IRF5 and c-MAF, cytokines IL-12, IL-10, and IL-6, as well as chemokines CXCL10 and CXCL1. Overall, our findings suggest ESAT-6 as being one of the effectors used by M.tb to induce the pro-inflammatory M1 phenotype at the primo-infection; a prerequisite step to promote granuloma formation and subsequently drive the phenotype switch of MΦ polarization from M1 to M2 at a later stage of the infection. Our study improves current knowledge regarding mechanisms of virulence of M.tb and may be helpful to develop novel tools targeting ESAT-6 for a better and more efficient treatment of tuberculosis.
-
Front Cell Infect Microbiol · Jan 2018
Anti-quorum Sensing Activities of Selected Coral Symbiotic Bacterial Extracts From the South China Sea.
The worldwide increase in antibiotic-resistant pathogens means that identification of alternative antibacterial drug targets and the subsequent development of new treatment strategies are urgently required. One such new target is the quorum sensing (QS) system. Coral microbial consortia harbor an enormous diversity of microbes, and are thus rich sources for isolating novel bioactive and pharmacologically valuable natural products. ⋯ From the chemical structure, the target compound (DL-homocysteine thiolactone) is an analog of the acyl-homoserine lactones (AHLs), and we presume that DL-homocysteine thiolactone outcompetes AHL in occupying the receptor and thereby inhibiting QS. Whole-genome sequence analysis of S. hominis D11 revealed the presence of predicted genes involved in the biosynthesis of homocysteine thiolactone. This study indicates that coral microbes are a resource bank for developing QS inhibitors and they will facilitate the discovery of new biotechnologically relevant compounds that could be used instead of traditional antibiotics.
-
Front Cell Infect Microbiol · Jan 2018
ReviewCould Heme Oxygenase-1 Be a New Target for Therapeutic Intervention in Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome?
Malaria is a serious disease and was responsible for 429,000 deaths in 2015. Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one of the main clinical complications of severe malaria; it is characterized by a high mortality rate and can even occur after antimalarial treatment when parasitemia is not detected. Rodent models of ALI/ARDS show similar clinical signs as in humans when the rodents are infected with murine Plasmodium. ⋯ Additionally, mice were protected against MA-ALI/ARDS after treatment with carbon monoxide- releasing molecules or with carbon monoxide, which is also released by the HO-1 activity. However, high HO-1 levels in inflammatory cells were associated with the respiratory burst of neutrophils and with an intensification of inflammation during episodes of severe malaria in humans. Here, we review the main aspects of HO-1 in malaria and ALI/ARDS, presenting the dual role of HO-1 and possibilities for therapeutic intervention by modulating this important enzyme.
-
Front Cell Infect Microbiol · Jan 2018
Influence of Micropatterned Grill Lines on Entamoeba histolytica Trophozoites Morphology and Migration.
Entamoeba histolytica, the causal agent of human amoebiasis, has two morphologically different phases: a resistant cyst and a trophozoite responsible for the invasion of the host tissues such as the colonic mucosa and the intestinal epithelium. During in vitro migration, trophozoites usually produce protuberances such as pseudopods and rarely filopodia, structures that have been observed in the interaction of trophozoites with human colonic epithelial tissue. To study the different membrane projections produced by the trophozoites, including pseudopods, filopodia, uropods, blebs, and others, we designed an induction system using erythrocyte extract or fibronectin (FN) in micropatterned grill lines (each micro-line containing multiple micro-portions of FN or erythrocyte extract) on which the trophozoites were placed in culture for migration assays. ⋯ It has been proposed that both physical forces and chemical signals are involved in the trophozoite motility and migration. However, the in vivo molecules that drive the chemotactic migration remain to be determined. We propose the present assay to study host molecules that guide chemotactic behavior because the method is highly reproducible, and a live image of cell movement and migration can be quantified.