Rapid emergence of antibiotic-resistant bacteria has made it harder for us to combat infectious diseases and to develop new antibiotics. The clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) system, as a bacterial adaptive immune system, is recognized as one of the new strategies for controlling antibioticresistant strains. The programmable Cas nuclease of this system used against bacterial genomic sequences could be lethal or could help reduce resistance of bacteria to antibiotics. Therefore, this study aims to review using the CRISPR-Cas system to promote sensitizing bacteria to antibiotics. We envision that CRISPR-Cas approaches may open novel ways for the development of smart antibiotics, which could eliminate multidrug-resistant (MDR) pathogens and differentiate between beneficial and pathogenic microorganisms. These systems can be exploited to quantitatively and selectively eliminate individual bacterial strains based on a sequence-specific manner, creating opportunities in the treatment of MDR infections, the study of microbial consortia, and the control of industrial fermentation.
Objective To determine if immediate compared to deferred initiation of antiretroviral therapy (ART) in healthy persons living with HIV (PLWH) had a more favorable impact on health-related quality of life (QOL), or self-assessed physical, mental and overall health status. Design QOL was measured in START (Strategic Timing of Antiretroviral Therapy), which randomized healthy ART naive PLWH with >500 CD4+ cells/μl from 35 countries to immediate versus deferred ART. Methods At baseline, months 4 and 12, then annually, participants completed a visual analogue scale (VAS) for “perceived current health” and the Short-Form 12-Item Health Survey version 2 from which were computed: (1) General health (GH) perception; (2) Physical Component Summary (PCS), and (3) Mental Component Summary (MCS); the VAS and GH were rated from 0=lowest to 100=highest. Results QOL at study entry was high (mean scores: VAS=80.9, GH=72.5, PCS=53.7, MCS=48.2). Over a mean follow-up of 3 years, changes in all QOL measures favored the immediate group (p<0.001); estimated differences were: VAS=1.9, GH=3.6, PCS=0.8, MCS=0.9. When QOL changes were assessed across various demographic and clinical subgroups, treatment differences continued to favor the immediate group. QOL was poorer in those experiencing primary outcomes; however, when excluding those with primary events, results remained favorable for immediate ART recipients. Conclusions In an international randomized trial in ART-naive participants with >500 CD4+ cells/μl, there were modest but significant improvements in self-assessed QOL among those initiating ART immediately compared to deferring treatment, supporting patient-perceived health benefits of initiating ART as soon as possible after an HIV diagnosis.
dMultilocus variable-number tandem-repeat analysis (MLVA) is efficient for routine typing and for investigating the genetic structures of natural microbial populations. Two distinct pathovars of Xanthomonas oryzae can cause significant crop losses in tropical and temperate rice-growing countries. Bacterial leaf streak is caused by X. oryzae pv. oryzicola, and bacterial leaf blight is caused by X. oryzae pv. oryzae. For the latter, two genetic lineages have been described in the literature. We developed a universal MLVA typing tool both for the identification of the three X. oryzae genetic lineages and for epidemiological analyses. Sixteen candidate variable-number tandem-repeat (VNTR) loci were selected according to their presence and polymorphism in 10 draft or complete genome sequences of the three X. oryzae lineages and by VNTR sequencing of a subset of loci of interest in 20 strains per lineage. The MLVA-16 scheme was then applied to 338 strains of X. oryzae representing different pathovars and geographical locations. Linkage disequilibrium between MLVA loci was calculated by index association on different scales, and the 16 loci showed linear Mantel correlation with MLSA data on 56 X. oryzae strains, suggesting that they provide a good phylogenetic signal. Furthermore, analyses of sets of strains for different lineages indicated the possibility of using the scheme for deeper epidemiological investigation on small spatial scales. M olecular typing of pathogen populations is essential to gain insight into their genetic diversity and population dynamics in order to elaborate efficient strategies for disease control (1, 2). In agricultural systems, pests are ideally controlled by integrated approaches, including eradication or treatment of diseased organisms and planting of resistant varieties. However, the durability of resistance can be challenged if pathogen diversity is significant. Importantly, gene flow between pathogen populations can facilitate the breakdown of resistance in crop plants (3). Hence, efficient and precise molecular-typing tools for identifying strains and differentiating among related bacterial isolates are essential for microevolutionary reconstruction as a population genetics approach for integrated plant protection.Rice, one of the major crops worldwide, is affected by two bacterial diseases that are caused by strains of Xanthomonas oryzae, bacterial leaf blight (BLB), caused by X. oryzae pv. oryzae, and bacterial leaf streak (BLS), caused by X. oryzae pv. oryzicola. Collectively, these two diseases cause significant yield losses in tropical and temperate rice-growing areas. X. oryzae pv. oryzae colonizes xylem vessels upon entry into the vascular system. X. oryzae pv. oryzicola infects the plant via natural openings and colonizes the mesophyll (4). Genomes of members of both pathovars have been sequenced; however, the determinants of tissue specificity are still largely unknown (5, 6). While X. oryzae pv. oryzicola has been shown to be seedborne and seed transmitted (7,8), the evidenc...
Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.
Bacterial leaf streak (BLS) caused by Xanthomonas oryzae pv. oryzicola was first reported in Africa in the 1980s. Recently, a substantial reemergence of this disease was observed in West Africa. Samples were collected at various sites in five and three different rice-growing regions of Burkina Faso and Mali, respectively. Sixty-seven X. oryzae pv. oryzicola strains were isolated from cultivated and wild rice varieties and from weeds showing BLS symptoms. X. oryzae pv. oryzicola strains were evaluated for virulence on rice and showed high variation in lesion length on a susceptible cultivar. X. oryzae pv. oryzicola strains were further characterized by multilocus sequence analysis (MLSA) using six housekeeping genes. Inferred dendrograms clearly indicated different groups among X. oryzae pv. oryzicola strains. Restriction fragment length polymorphism analysis using the transcriptional activator like effector avrXa7 as probe resulted in the identification of 18 haplotypes. Polymerase chain reaction-based analyses of two conserved type III effector (T3E) genes (xopAJ and xopW) differentiated the strains into distinct groups, with xopAJ not detected in most African X. oryzae pv. oryzicola strains. XopAJ functionality was confirmed by leaf infiltration on 'Kitaake' rice Rxo1 lines. Sequence analysis of xopW revealed four groups among X. oryzae pv. oryzicola strains. Distribution of 43 T3E genes shows variation in a subset of X. oryzae pv. oryzicola strains. Together, our results show that African X. oryzae pv. oryzicola strains are diverse and rapidly evolving, with a group endemic to Africa and another one that may have evolved from an Asian strain.
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