Elite controllers microbiome: unraveling the mystery of association and causation.

PURPOSE OF REVIEW: To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions. RECENT FINDINGS: EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection. SUMMARY: An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.

Pulmonary comorbidities in people with HIV- the microbiome connection.

PURPOSE OF REVIEW: To report recent evidence on associations between human microbiome, particularly airway and gut, and pulmonary comorbidities in people with HIV (PWH). Furthermore, we explore how changes in the microbiome may contribute to pulmonary immune dysregulation and higher rates of pulmonary comorbidities among PWH. Finally, we propose future directions in the field. RECENT FINDINGS: Increased risk of pulmonary comorbidities and rapid lung function decline have been reported in even well treated PWH. Altered microbiota profiles have been reported in PWH with pulmonary comorbidities and rapid lung function decline as compared to those without. The most consistent data have been the association between HIV-related pulmonary comorbidities, lung and oral microbiota dysbiosis, which has been also associated with distinct respiratory mucosal inflammatory profiles and short-term mortality. However, a possible causal link remains to be elucidated. SUMMARY: Associations between the lung and oral microbiome, HIV-associated pulmonary comorbidities and rapid lung function decline have been reported in recent studies. Yet the underlying mechanism underpinning the observed associations is largely unknown and substantial knowledge gaps remain. Future research is warranted to unveil the role and mechanism of human microbiome from different anatomical compartments in relation to pulmonary comorbidities in PWH.

Prevalence and Characteristics of Plasmid-Encoded Serine Protease EspP in Clinical Shiga Toxin-Producing Escherichia coli Strains from Patients in Sweden.

Shiga toxin-producing Escherichia coli (STEC) infection can cause a broad spectrum of symptoms spanning from asymptomatic shedding to mild and bloody diarrhea (BD) and even life-threatening hemolytic-uremic syndrome (HUS). As a member of the serine protease autotransporters of Enterobacteriaceae (SPATE) family, EspP has the ability to degrade human coagulation factor V, leading to mucosal bleeding, and also plays a role in bacteria adhesion to the surface of host cells. Here, we investigated the prevalence and genetic diversity of espP among clinical STEC isolates from patients with mild diarrhea, BD, and HUS, as well as from asymptomatic individuals, and assessed the presence of espP and its subtypes in correlation to disease severity. We found that 130 out of 239 (54.4%) clinical STEC strains were espP positive, and the presence of espP was significantly associated with BD, HUS, and O157:H7 serotype. Eighteen unique espP genotypes (GTs) were identified and categorized into four espP subtypes, i.e., espPα (119, 91.5%), espPγ (5, 3.8%), espPδ (4, 3.1%), and espPε (2, 1.5%). espPα was widely distributed, especially in strains from patients with BD and HUS, and correlated with serotype O157:H7. Serogroup O26, O145, O121, and O103 strains carried espPα only. Ten GTs were identified in espPα, and espPα/GT2 was significantly associated with severe disease, i.e., BD and HUS. Additionally, espP was strongly linked to the presence of eae gene, and the coexistence of espPα and stx2/stx2a + stx2c was closely related to HUS status. To sum up, our data demonstrated a high prevalence and genetic diversity of the espP gene in clinical STEC strains in Sweden and revealed an association between the presence of espP, espP subtypes, and disease severity. espP, particularly the espPα subtype, was prone to be present in more virulent STEC strains, e.g., "top-six" serotypes strains.

Genetic Characterization of Intimin Gene (eae) in Clinical Shiga Toxin-Producing Escherichia coli Strains from Pediatric Patients in Finland.

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, ß3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5-17 years, while ß3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children.

Genetic Diversity and Expression of Intimin in Escherichia albertii Isolated from Humans, Animals, and Food.

Escherichia albertii (E. albertii) is an emerging diarrheagenic pathogen associated with sporadic infections and human gastroenteric outbreaks. The eae gene, which encodes intimin in the locus of enterocyte effacement (LEE) operon, contributes to the establishment of the attaching and effacing (A/E) lesion. Increasing collection of E. albertii strains from various sources has resulted in a rapid increase in the number of eae subtypes. This study systematically investigated the prevalence and genetic diversity of eae among E. albertii strains isolated from humans, animals, and food. The eae gene was present in 452/459 (98.5%) strains and 23 subtypes were identified including two novel subtypes, named eae-α11 and η3. The eae-σ subtype was the most predominant among humans, animals, and food-derived strains, while eae-γ3, τ, and α11 were unique in human-derived strains. Additionally, the LEE island was also analyzed at genomic, transcriptional, and functional levels through genomic analysis, quantitative reverse transcription PCR, and HEp-2 cell adherence assays, respectively. The eae transcript levels were variable and associated with eae subtypes. Three different adherence patterns, including localized adherence-like (LAL), diffuse adherence (DA), and detachment (DE), were observed among E. albertii strains. This study demonstrated a high diversity of functional intimin in E. albertii strains isolated from humans, animals, and food. Further in vivo and in vitro studies are warranted to better elucidate the role of intimin or LEE in different genetic backgrounds.