Neisseria gonorrhoeae ST-1901 in Rio de Janeiro from 2006 to 2022: Phylogeny and antimicrobial resistance evolution of a well-succeeded pathogen.

Neisseria gonorrhoeae is a global threat to public health due to the accumulation of antimicrobial resistance mechanisms. ST-1901 is an internationally important sequence type (ST) because of its high incidence and the usual occurrence of chromosomally determined resistance. In this study, we describe the evolution of the ST-1901 and its single locus variants in Rio de Janeiro from 2006 to 2022. We analyzed 82 N. gonorrhoeae isolates according to antimicrobial susceptibility profile, resistance mechanisms, molecular typing, and phylogenetics. Six different single locus variants were detected. Phylogenetic analysis identified five clades, which share similar characteristics. Resistance rates for penicillin and tetracycline decreased due to the lower occurrence of resistance plasmids, but intermediary resistance to penicillin rose. Resistance to ciprofloxacin remained high throughout all clades and the years of the study. Regarding resistance to azithromycin, alterations in mtrR promoter and gene, and 23S rRNA encoding gene rrl were detected, with a notable rise in the incidence of C2611T mutations in more recent years occurring in four of five clades. In contrast, ß-lactam resistance associated penA 34 mosaic was found only in one persisting clade (Clade D), and unique G45D and A39T mutations in mtrR gene and its promoter (Nm-Like) were found only in Clade B. Taken together, these data suggest that ST-1901, a persistently circulating lineage of N. gonorrhoeae in Rio de Janeiro, has undergone changes over the years and may evolve to develop resistance to the current recommended dual therapy adopted in Brazil, namely, ceftriaxone and azithromycin.

Evidence for Clonally Associated Increasing Rates of Azithromycin Resistant Neisseria gonorrhoeae in Rio de Janeiro, Brazil.

Azithromycin is one of the drugs used in the combined therapy for syndromic treatment of gonorrhoea in many countries, including Brazil. Our research group, which receives isolates from clinical laboratories since 2006, has detected, after 2016, a tendency of rising rates of azithromycin resistance, with isolates showing higher minimal inhibitory concentrations (MICs) than those previously reported in this country. In this study, we report the susceptibility to azithromycin of 93 N. gonorrhoeae isolates obtained between 2014 and 2017. Strains with MIC ≥2 µg/mL were characterized according to azithromycin resistance mechanisms and strain typing. Results indicate that azithromycin resistance has emerged in all these years in unrelated MLST-STs, but after 2016 a clonal complex connected with ST1901 has been more frequently detected, grouping isolates with MIC varying from 2 to 64 µg/mL, with DelA mutations at the mtrR promoter region associated or not with mutations at rrl alleles. High rates of azithromycin resistance may compromise the use of this drug in the combined therapy with ceftriaxone. Inclusion of Rio de Janeiro in the Brazilian gonococcal surveillance program is important to evaluate if this data indicates an epidemiological phenomenon in the country.

Role of Rb during Neurogenesis and Axonal Guidance in the Developing Olfactory System.

The Retinoblastoma protein, Rb, was shown to regulate distinct aspects of neurogenesis in the embryonic and adult brain besides its primary role in cell cycle control. It is still unknown, however, whether Rb is required for tissue morphogenesis and the establishment of synaptic connections between adjacent tissues during development. We have investigated here the role of Rb during development of the olfactory system (OS), which heavily relies on reciprocal interactions between the olfactory epithelium (OE) and the olfactory bulb (OB). We show that mice carrying a telencephalic-specific deletion of Rb display several neurogenic defects in the OS during late development. In the OE, loss of Rb leads to ectopic proliferation of late-born progenitors (Tuj-1+), abnormal radial migration and terminal maturation of olfactory sensory neurons (OSNs). In the OB, deletion of Rb causes severe lamination defects with loss of clear boundaries between distinct layers. Importantly, starting around E15.5 when OB glomerulogenesis is initiated, many OSNs axons that project along the olfactory nerve layer (ONL) fail to properly innervate the nascent bulb, thus resulting in partial loss of connectivity between OE-OB and gradual neuronal degeneration in both tissues peaking at birth. This deficiency correlates with deregulated expressions of two key chemo-repellant molecules, Robo2/Slit1 and Nrp2/Sema3F that control the formation of dorsal-ventral topographic map of OSNs connections with OB glomeruli. This study highlights a critical requirement for Rb during neurogenesis and the establishment of proper synaptic connections inside the OS during development.

Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb.

Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons.

Seroprevalence of IgG and IgM anti-SARS-CoV-2 among voluntary blood donors in Rio de Janeiro, Brazil

Background: In Brazil, mathematical models for derivingestimates and projections of COVID-19 cases have been developed without data on asymptomatic SARS-CoV-2 infection. We estimated the seroprevalence of antibodies to SARS-CoV-2 among blood donors in the State of Rio de Janeiro. Methods: Data were collected on 2,857 blood donors from April 14 to 27, 2020. We report the crude prevalence of antibodies to SARS-CoV-2, the weighted prevalence by the total state population, and adjusted prevalence estimates for test sensitivity and specificity. To establish the correlates of SARS-CoV-2 prevalence, we used logistic regression models. The analysis included period and site of blood collection, sociodemographic characteristics, and place of residence. Results: The proportion of SARS-Cov-2 positive tests without any adjustment was 4.0% (95% CI 3.3-4.7%), and the weighted prevalence was 3.8% (95% CI 3.1-4.5%). Further adjustment by test sensitivity and specificity produced lower estimates, 3.6% (95% CI 2.7-4.4%) and 3.3% (95% CI 2.6-4.1%), respectively. The variable most significantly associated with the crude prevalence was the period of blood collection: the later the period, the higher the prevalence. Regarding socio-demographic characteristics, the younger the blood donors, the higher the prevalence, and the lower the educational level, the higher the odds of a positive SARS-Cov-2 antibody. Similar results were found for the weighted prevalence. Discussion: Although our findings resulted from a convenience sample, they match some basic premises: the increasing trend over time, since the epidemic curve in the state is still on the rise; the higher prevalence among the youngest who are more likely to circulate; and the higher prevalence among the less educated as they have more difficulties in following the social distancing recommendations. Despite the study limitations, it is possible to infer that protective levels of natural herd immunity to SARS-CoV-2 are far from being reached in Rio de Janeiro. (AU)