The first taxonomic and functional characterization of human CAVD-associated microbiota
January 13, 2023
Calcific aortic valve disease (CAVD) is the most common heart valve disorder, defined by a remodeling multistep process. In this study, we aimed to investigate and characterize the presence of valvular microbiota and the associated immune response in human CAV samples originating from two European populations.
Cellular cholesterol licenses Legionella pneumophila intracellular replication in macrophages
December 6, 2022
Host membranes are inherently critical for niche homeostasis of vacuolar pathogens such as Legionella. One membrane component that is often subverted by vacuolar bacteria is cholesterol. We provide experimental evidence that cellular cholesterol promotes L. pneumophila replication within a membrane bound organelle in infected macrophages.
DadY (PA5303) is required for fitness of Pseudomonas aeruginosa when growth is dependent on alanine catabolism
November 22, 2022
Pseudomonas aeruginosa inhabits diverse environmental niches that can have varying nutrient composition. The ubiquity of this organism is facilitated by a metabolic strategy that preferentially utilizes low-energy, non-fermentable organic acids, such as amino acids, rather than the high-energy sugars preferred by many other microbes. The amino acid alanine is among the preferred substrates of P. aeruginosa. The dad locus encodes the constituents of the alanine catabolic pathway of P. aeruginosa. Physiological roles for DadR (AsnC-type transcriptional activator), DadX (alanine racemase), and DadA (D-amino acid dehydrogenase) have been defined in this pathway. An additional protein, PA5303, is encoded in the dad locus in P. aeruginosa. PA5303 is a member of the ubiquitous Rid protein superfamily and is designated DadY based on the data presented herein. (...)
Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy
November 15, 2022
Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.
Multiple genome analysis of Candida glabrata clinical isolates renders new insights into genetic diversity and drug resistance determinants
October 13, 2022
The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The(...)
Occurrence and potential mechanism of holin-mediated non-lytic protein translocation in bacteria
September 23, 2022
Holins are generally believed to generate large membrane lesions that permit the passage of endolysins across the cytoplasmic membrane of prokaryotes, ultimately resulting in cell wall degradation and cell lysis. However, there are more and more examples known for non-lytic holin-dependent secretion of proteins by bacteria, indicating that holins somehow can transport proteins without causing large membrane lesions. Phage-derived holins can be used for a non-lytic endolysin translocation to permeabilize the cell wall for the passage of secreted proteins. In addition, clostridia, which do not possess the Tat pathway for transport of folded proteins, most likely employ non-lytic holin-mediated transport also for secretion of toxins and bacteriocins that are incompatible with the general Sec pathway. The mechanism for non-lytic holin-mediated transport is (...)
Flagellated bacterial porter for in situ tumor vaccine
August 24, 2022
Cancer immunotherapy, which use the own immune system to attack tumors, are increasingly popular treatments. But, due to the tumor immunosuppressive microenvironment, the antigen presentation in the tumor is limited. Recently, a growing number of people use bacteria to stimulate the body's immunity for tumor treatment due to bacteria themselves have a variety of elements that activate Toll-like receptors. Here, we discuss the use of motility of flagellate bacteria to transport antigens to the tumor periphery to activate peritumoral dendritic cells to enhance the effect of in situ tumor vaccines.
The rise of Candida auris: from unique traits to co-infection potential
August 1, 2022
Candida auris is a multidrug resistant (MDR) fungal pathogen with a crude mortality rate of 30-60%. First identified in 2009, C. auris has been rapidly rising to become a global risk in clinical settings and was declared an urgent health threat by the Centers for Disease Control and Prevention (CDC). A concerted global action is thus needed to successfully tackle the challenges created by this emerging fungal pathogen. In this brief article, we underline the importance of unique virulence traits, including its easy transformation, its persistence outside the host and its resilience against multiple cellular stresses, as well as of environmental factors that have mainly contributed to the rise of this superbug.