Biosynthetic gene clusters with biotechnological applications in novel Antarctic isolates from Actinomycetota.

Actinomycetota have been widely described as valuable sources for the acquisition of secondary metabolites. Most microbial metabolites are produced via metabolic pathways encoded by biosynthetic gene clusters (BGCs). Although many secondary metabolites are not essential for the survival of bacteria, they play an important role in their adaptation and interactions within microbial communities. This is how bacteria isolated from extreme environments such as Antarctica could facilitate the discovery of new BGCs with biotechnological potential. This study aimed to isolate rare Actinomycetota strains from Antarctic soil and sediment samples and identify their metabolic potential based on genome mining and exploration of biosynthetic gene clusters. To this end, the strains were sequenced using Illumina and Oxford Nanopore Technologies platforms. The assemblies were annotated and subjected to phylogenetic analysis. Finally, the BGCs present in each genome were identified using the antiSMASH tool, and the biosynthetic diversity of the Micrococcaceae family was evaluated. Taxonomic annotation revealed that seven strains were new and two were previously reported in the NCBI database. Additionally, BGCs encoding type III polyketide synthases (T3PKS), beta-lactones, siderophores, and non-ribosomal peptide synthetases (NRPS) have been identified, among others. In addition, the sequence similarity network showed a predominant type of BGCs in the family Micrococcaceae, and some genera were distinctly grouped. The BGCs identified in the isolated strains could be associated with applications such as antimicrobials, anticancer agents, and plant growth promoters, among others, positioning them as excellent candidates for future biotechnological applications and innovations. KEY POINTS: • Novel Antarctic rare Actinomycetota strains were isolated from soil and sediments • Genome-based taxonomic affiliation revealed seven potentially novel species • Genome mining showed metabolic potential for novel natural products.

Bruna P ，Núñez-Montero K ，Contreras MJ ，Leal K ，García M ，Abanto M ，Barrientos L ... -  《-》

Defining the optimum strategy for identifying adults and children with coeliac disease: systematic review and economic modelling.

Elwenspoek MM ，Thom H ，Sheppard AL ，Keeney E ，O'Donnell R ，Jackson J ，Roadevin C ，Dawson S ，Lane D ，Stubbs J ，Everitt H ，Watson JC ，Hay AD ，Gillett P ，Robins G ，Jones HE ，Mallett S ，Whiting PF ... -  《-》

Qualitative evidence synthesis informing our understanding of people's perceptions and experiences of targeted digital communication.

Health communication is an area where changing technologies, particularly digital technologies, have a growing role to play in delivering and exchanging health information between individuals, communities, health systems, and governments.[1] Such innovation has the potential to strengthen health systems and services, with substantial investments in digital health already taking place, particularly in low‐ and middle‐income countries. Communication using mobile phones is an important way of contacting individual people and the public more generally to deliver and exchange health information. Such technologies are used increasingly in this capacity, but poor planning and short‐term projects may be limiting their potential for health improvement. The assumption that mobile devices will solve problems that other forms of communication have not is also prevalent. In this context, understanding people's views and experiences may lead to firmer knowledge on which to build better programs. A qualitative evidence synthesis by Heather Ames and colleagues on clients' perceptions and experiences of targeted digital communication focuses on a particular type of messaging – targeted messages from health services delivered to particular group(s) via mobile devices, in this case looking at communicating with pregnant women and parents of young children, and with adults and teenagers about sexual health and family planning.[2] These areas of reproductive, maternal, newborn, child, and adolescent health (RMNCAH) are where important gains have been made worldwide, but there remains room for improvement. Ames and colleagues sought to examine and understand people's perceptions and experiences of using digital targeted client communication. This might include communication in different formats and with a range of purposes related to RMNCAH – for example, receiving text message reminders to take medicines (e.g. HIV medicines) or go to appointments (such as childhood vaccination appointments), or phone calls offering information or education (such as about breastfeeding or childhood illnesses), support (e.g. providing encouragement to change behaviours) or advice (such as advising about local healthcare services). These communication strategies have the potential to improve health outcomes by communicating with people or by supporting behaviour change. However, changing people's health behaviours to a significant and meaningful degree is notoriously challenging and seldom very effective across the board. There are a multitude of systematic reviews of interventions aiming to change behaviours of both patients and providers, with the overall objective of improving health outcomes – many of which show little or no average effects across groups of people.[3] This evidence synthesis is therefore important as it may help to understand why communicating with people around their health might (or might not) change behaviours and improve consequent health outcomes. By examining the experiences and perspectives of those receiving the interventions, this qualitative evidence synthesis allows us to better understand the interventions' acceptability and usefulness, barriers to their uptake, and factors to be considered when planning implementation. The synthesis looked at 35 studies from countries around the world, focussing on communication related to RMNCAH. Of the 35 studies, 16 were from high‐income countries, mainly the United States, and 19 were from low‐ or middle‐income countries, mainly African countries. Many of the studies presented hypothetical scenarios. The findings from the synthesis are mixed and give us a more nuanced picture of the role of targeted digital communication. People receiving targeted digital communications from health services often liked and valued these contacts, feeling supported and connected by them. However, some also reported problems with the use of these technologies, which may represent barriers to their use. These included practical or technical barriers like poor network or Internet access, as well as cost, language, technical literacy, reading or issues around confidentiality, especially where personal health conditions were involved. Access to mobile phones may also be a barrier, particularly for women and adolescents who may have to share or borrow a phone or who have access controlled by others. In such situations it may be difficult to receive communications or to maintain privacy of content. The synthesis also shows that people's experiences of these interventions are influenced by factors such as the timing of messages, their frequency and content, and their trust in the sender. Identifying key features of such communications by the people who use them might therefore help to inform future choices about how and when such messaging is used. The authors used their knowledge from 25 separate findings to list ten implications for practice. This section of the review is hugely valuable, making a practical contribution to assist governments and public health agencies wishing to develop or improve their delivery of digital health. The implications serve as a list of points to consider, including issues of access (seven different aspects are considered), privacy and confidentiality, reliability, credibility and trust, and responsiveness to the needs and preferences of users. In this way, qualitative evidence is building a picture of how to better communicate with people about health. For example, an earlier 2017 Cochrane qualitative evidence synthesis by Ames, Glenton and Lewin on parents' and informal caregivers' views and experiences of communication about routine childhood vaccination provides ample evidence that may help program managers to deliver or plan communication interventions in ways that are responsive to and acceptable to parents.[4] The qualitative synthesis method, therefore, puts a spotlight on how people's experiences of health and health care in the context of their lives may lead to the design of better interventions, as well as to experimental studies which take more account of the diversity that exists in people's attitudes and decision‐making experiences.[5] In the case of this qualitative evidence synthesis by Ames and colleagues, the method pulled together a substantial body of research (35 data‐rich studies were sampled from 48 studies identified, with the high‐to‐moderate confidence in the evidence for 13 of the synthesized findings). The evidence from this review can inform the development of interventions, and the design of trials and their implementation. While waiting for such new trials or trial evidence on effects to emerge, decision‐makers can build their programs on the highly informative base developed by this review. This qualitative evidence synthesis, alongside other reviews, has informed development by the World Health Organization of its first guideline for using digital technologies for health systems strengthening,[1, 6] part of a comprehensive program of work to better understand and support implementation of such new technologies.

Ryan R ，Hill S 《Cochrane Database of Systematic Reviews》

Biosynthetic potential of the sediment microbial subcommunities of an unexplored karst ecosystem and its ecological implications.

Microbial communities from various environments have been studied in the quest for new natural products with a broad range of applications in medicine and biotechnology. We employed an enrichment method and genome mining tools to examine the biosynthetic potential of microbial communities in the sediments of a coastal sinkhole within the karst ecosystem of the Yucatán Peninsula, Mexico. Our investigation led to the detection of 203 biosynthetic gene clusters (BGCs) and 55 secondary metabolites (SMs) within 35 high-quality metagenome-assembled genomes (MAGs) derived from these subcommunities. The most abundant types of BGCs were Terpene, Nonribosomal peptide-synthetase, and Type III polyketide synthase. Some of the in silico identified BGCs and SMs have been previously reported to exhibit biological activities against pathogenic bacteria and fungi. Others could play significant roles in the sinkhole ecosystem, such as iron solubilization and osmotic stress protection. Interestingly, 75% of the BGCs showed no sequence homology with bacterial BGCs previously reported in the MiBIG database. This suggests that the microbial communities in this environment could be an untapped source of genes encoding novel specialized compounds. The majority of the BGCs were identified in pathways found in the genus Virgibacillus, followed by Sporosarcina, Siminovitchia, Rhodococcus, and Halomonas. The latter, along with Paraclostridium and Lysinibacillus, had the highest number of identified BGC types. This study offers fresh insights into the potential ecological role of SMs from sediment microbial communities in an unexplored environment, underscoring their value as a source of novel natural products.

Suárez-Moo P ，Prieto-Davó A 《MicrobiologyOpen》

RETRACTED: Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial.

Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads. French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/locate/withdrawalpolicy). Concerns have been raised regarding this article, the substance of which relate to the articles' adherence to Elsevier's publishing ethics policies and the appropriate conduct of research involving human participants, as well as concerns raised by three of the authors themselves regarding the article's methodology and conclusions. Elsevier's Research Integrity and Publishing Ethics Team, in collaboration with the journal's co-owner, the International Society of Antimicrobial Chemotherapy (ISAC), and with guidance from an impartial field expert acting in the role of an independent Publishing Ethics Advisor, Dr. Jim Gray, Consultant Microbiologist at the Birmingham Children's and Women's Hospitals, U.K., conducted an investigation and determined that the below points constituted cause for retraction: • The journal has been unable to confirm whether any of the patients for this study were accrued before ethical approval had been obtained. The ethical approval dates for this article are stated as being 5th and 6th of March 2020 (ANSM and CPP respectively), while the article states that recruitment began in “early March”. The 17th author, Prof. Philippe Brouqui, has confirmed that the start date for patient accrual was 6th March 2020. The journal has not been able to establish whether all patients could have entered into the study in time for the data to have been analysed and included in the manuscript prior to its submission on the 20th March 2020, nor whether all patients were enrolled in the study upon admission as opposed to having been hospitalised for some time before starting the treatment described in the article. Additionally, the journal has not been able to establish whether there was equipoise between the study patients and the control patients. • The journal has not been able to establish whether the subjects in this study should have provided informed consent to receive azithromycin as part of the study. The journal has concluded that that there is reasonable cause to conclude that azithromycin was not considered standard care at the time of the study. The 17th author, Prof. Philippe Brouqui has attested that azithromycin treatment was not, at the time of the study, an experimental treatment but a possible treatment for, or preventative measure against, bacterial superinfections of viral pneumonia as described in section 2.4 of the article, and as such the treatment should be categorised as standard care that would not require informed consent. This does not fully address the journal's concerns around the use of azithromycin in the study. In section 3.1 of the article, it is stated that six patients received azithromycin to prevent (rather than treat) bacterial superinfection. All of these were amongst the patients who also received hydroxychloroquine (HCQ). None of the control patients are reported to have received azithromycin. This would indicate that only patients in the HCQ arm received azithromycin, all of whom were in one center. The recommendations for use of macrolides in France at the time the study was conducted indicate that azithromycin would not have been a logical agent to use as first-line prophylaxis against pneumonia due to the frequency of macrolide resistance amongst bacteria such as pneumococci. These two points suggest that azithromycin would not have been standard practice across southern France at the time the study was conducted and would have required informed consent. • Three of the authors of this article, Dr. Johan Courjon, Prof. Valérie Giordanengo, and Dr. Stéphane Honoré have contacted the journal to assert their opinion that they have concerns regarding the presentation and interpretation of results in this article and have stated they no longer wish to see their names associated with the article. • Author Prof. Valérie Giordanengo informed the journal that while the PCR tests administered in Nice were interpreted according to the recommendations of the national reference center, it is believed that those carried out in Marseille were not conducted using the same technique or not interpreted according to the same recommendations, which in her opinion would have resulted in a bias in the analysis of the data. This raises concerns as to whether the study was partially conducted counter to national guidelines at that time. The 17th author, Prof. Philippe Brouqui has attested that the PCR methodology was explained in reference 17 of the article. However, the article referred to by reference 17 describes several diagnostic approaches that were used (one PCR targeting the envelope protein only; another targeting the spike protein; and three commercially produced systems by QuantiNova, Biofire, and FTD). This reference does not clarify how the results were interpreted. It has also been noted during investigation of these concerns that only 76% (19/25) of patients were viral culture positive, resulting in uncertainty in the interpretation of PCR reports as has been raised by Prof. Giordanengo. As part of the investigation, the corresponding author was contacted and asked to provide an explanation for the above concerns. No response has been received within the deadline provided by the journal. Responses were received by the 3rd and 17th authors, Prof. Philippe Parola and Prof. Philippe Brouqui, respectively, and were reviewed as part of the investigation. These two authors, in addition to 1st author Dr. Philippe Gautret, 13th author Prof. Philippe Colson, and 15th author Prof. Bernard La Scola, disagreed with the retraction and dispute the grounds for it. Having followed due process and concluded the aforementioned investigation and based on the recommendation of Dr. Jim Gray acting in his capacity as independent Publishing Ethics Advisor, the co-owners of the journal (Elsevier and ISAC) have therefore taken the decision to retract the article.

Gautret P ，Lagier JC ，Parola P ，Hoang VT ，Meddeb L ，Mailhe M ，Doudier B ，Courjon J ，Giordanengo V ，Vieira VE ，Tissot Dupont H ，Honoré S ，Colson P ，Chabrière E ，La Scola B ，Rolain JM ，Brouqui P ，Raoult D ... -  《-》