Sheeba S Manoharan-Basil

Bio: Sheeba S Manoharan-Basil is an academic researcher from Institute of Tropical Medicine Antwerp. The author has contributed to research in topics: Neisseria gonorrhoeae & Medicine. The author has an hindex of 5, co-authored 16 publications receiving 56 citations.

WGS of Commensal Neisseria Reveals Acquisition of a New Ribosomal Protection Protein (MsrD) as a Possible Explanation for High Level Azithromycin Resistance in Belgium

Abstract: In this study, we characterized all oropharyngeal and anorectal isolates of Neisseria spp in a cohort of men who have sex with men This resulted in a panel of pathogenic Neisseria (N gonorrhoeae [n = 5] and N meningitidis [n = 5]) and nonpathogenic Neisseria (N subflava [n = 11], N mucosa [n = 3] and N oralis [n = 2]) A high proportion of strains in this panel were resistant to azithromycin (18/26) and ceftriaxone (3/26) Whole genome sequencing (WGS) of these strains identified numerous mutations that are known to confer reduced susceptibility to azithromycin and ceftriaxone in N gonorrhoeae The presence or absence of these known mutations did not explain the high level resistance to azithromycin (>256 mg/L) in the nonpathogenic isolates (8/16) After screening for antimicrobial resistance (AMR) genes, we found a ribosomal protection protein, Msr(D), in these highly azithromycin resistant nonpathogenic strains The complete integration site originated from Streptococcus pneumoniae and is associated with high level resistance to azithromycin in many other bacterial species This novel AMR resistance mechanism to azithromycin in nonpathogenic Neisseria could be a public health concern if it were to be transmitted to pathogenic Neisseria This study demonstrates the utility of WGS-based surveillance of nonpathogenic Neisseria

Molecular pathways to high-level azithromycin resistance in Neisseria gonorrhoeae.

Abstract: Background The prevalence of azithromycin resistance in Neisseria gonorrhoeae is increasing in numerous populations worldwide. Objectives To characterize the genetic pathways leading to high-level azithromycin resistance. Methods A customized morbidostat was used to subject two N. gonorrhoeae reference strains (WHO-F and WHO-X) to dynamically sustained azithromycin pressure. We tracked stepwise evolution of resistance by whole genome sequencing. Results Within 26 days, all cultures evolved high-level azithromycin resistance. Typically, the first step towards resistance was found in transitory mutations in genes rplD, rplV and rpmH (encoding the ribosomal proteins L4, L22 and L34 respectively), followed by mutations in the MtrCDE-encoded efflux pump and the 23S rRNA gene. Low- to high-level resistance was associated with mutations in the ribosomal proteins and MtrCDE efflux pump. However, high-level resistance was consistently associated with mutations in the 23S ribosomal RNA, mainly the well-known A2059G and C2611T mutations, but also at position A2058G. Conclusions This study enabled us to track previously reported mutations and identify novel mutations in ribosomal proteins (L4, L22 and L34) that may play a role in the genesis of azithromycin resistance in N. gonorrhoeae.

Cultural Drivers of Antibiotic Consumption in High-Income Countries: A Global Ecological Analysis

Abstract: Background: Previous studies evaluating the cultural and structural factors underpinning the large variations in the consumption of antibiotics in high-income countries have reached different conclusions. Some studies have found that corruption plays a dominant role, whereas other studies have concluded that cultural factors such as the degree of uncertainty avoidance (UA) and performance-orientation versus cooperation-orientation (POCO) are more important. These studies have been limited to Europe, and we, therefore, aimed to expand this analysis to all high-income countries with available data. Methods: Using antibiotic consumption data from the IQVIA MIDAS database, linear regression models were constructed with country-level cephalosporin, fluoroquinolone, and macrolide consumption (defined daily doses/1,000 population/year) as the outcome variables and country-specific scores of UA and POCO (obtained from the Hofstede Index), gross domestic product/capita, world region and markers of effective governance (Control of Corruption and Regulatory Quality extracted from the World Bank data) as the explanatory variables. All data, excluding the Hofstede Indices, used country-level averages for the years 2013 to 2015. Results: Complete data were available for 37 countries from 4 world regions. Consumption of cephalosporins, macrolides, and fluoroquinolones was associated with POCO and UA, but not the markers of effective governance. In the case of macrolide consumption, the association with UA narrowly missed statistical significance. Repeat analyses limited to first European countries and second to non-European countries revealed similar findings. Conclusions: More thought should be given to construct antibiotic stewardship campaigns that are tailored to the local extent of UA and POCO.

Is There a Resistance Threshold for Macrolide Consumption? Positive Evidence from an Ecological Analysis of Resistance Data from Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium.

Abstract: If we were to keep macrolide consumption below a certain threshold, would this reduce the probability of macrolide resistance emerging? No study that we are aware of has addressed this question. We, therefore, assessed at a country level if there was a macrolide consumption threshold for the selection of a prevalence of macrolide resistance of over 5% in Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium. In this ecological-level analysis, we found evidence for a macrolide consumption threshold of 1.3 defined daily doses per 1,000 inhabitants per day (DID) for M. genitalium, 1.8 DID for T. pallidum, and 2.3 DID for S. pneumoniae. Our results provide further motivation for macrolide stewardship campaigns that strive to reduce macrolide consumption to levels below at least 2 DID.

Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome

Abstract: Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome “Running title : Long-term antibiotic impacts Hedvig Jakobsson 1,2 , Cecilia Jernberg 1 , Anders F Andersson 1,3 , Maria Sjolund-Karlsson 1 , Janet K Jansson 4,5* , and Lars Engstrand 1,2 Department of Bacteriology, Swedish Institute for Infectious Disease Control, Stockholm, Sweden, 2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden, 3 Limnology/Department of Ecology and Evolution, Evolutionary Biology Centre, Uppsala University, Sweden, 4 Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden, Berkeley National Laboratory, Berkeley, CA, USA. Ecology Department, Lawrence phone number: +46 (8) 4572412; fax: +46-8-301797; email: hedvig.jakobsson@smi.se ∗Corresponding author. Mailing address: Department of Bacteriology, Swedish Institute for Infectious Disease Control, SE-171 82 Solna, Sweden. Phone: +46-8-4572415. Fax: 46-8- 301797. Email: lars.engstrand@smi.se Abbreviations: T-RFLP, terminal-restriction fragment length polymorphism; TRFs, terminal- restriction fragments; OTU, operational taxonomic unit; CA, correspondence analysis; erm, erythromycin resistance methylase. *Jansson's work is partially supported by the U.S. Department of Energy and Lawrence Berkeley National Laboratory under Contract No. DE-AC02-05CH11231.

Antibiotic Resistance: Moving From Individual Health Norms to Social Norms in One Health and Global Health.

Abstract: Antibiotic resistance is a problem for human health, and consequently, its study had been traditionally focused toward its impact for the success of treating human infections in individual patients (individual health). Nevertheless, antibiotic-resistant bacteria and antibiotic resistance genes are not confined only to the infected patients. It is now generally accepted that the problem goes beyond humans, hospitals, or long-term facility settings and that it should be considered simultaneously in human-connected animals, farms, food, water, and natural ecosystems. In this regard, the health of humans, animals, and local antibiotic-resistance-polluted environments should influence the health of the whole interconnected local ecosystem (One Health). In addition, antibiotic resistance is also a global problem; any resistant microorganism (and its antibiotic resistance genes) could be distributed worldwide. Consequently, antibiotic resistance is a pandemic that requires Global Health solutions. Social norms, imposing individual and group behavior that favor global human health and in accordance with the increasingly collective awareness of the lack of human alienation from nature, will positively influence these solutions. In this regard, the problem of antibiotic resistance should be understood within the framework of socioeconomic and ecological efforts to ensure the sustainability of human development and the associated human-natural ecosystem interactions.

Macrolide Resistance in Streptococcus Pneumoniae

Abstract: Streptococcus pneumoniae is a common commensal and an opportunistic pathogen. Suspected pneumococcal upper respiratory infections and pneumonia are often treated with macrolide antibiotics. Macrolides are bacteriostatic antibiotics and inhibit protein synthesis by binding to the 50S ribosomal subunit. The widespread use of macrolides is associated with increased macrolide resistance in S. pneumoniae, and the treatment of pneumococcal infections with macrolides may be associated with clinical failures. In S. pneumoniae, macrolide resistance is due to ribosomal dimethylation by an enzyme encoded by erm(B), efflux by a two-component efflux pump encoded by mef (E)/mel(msr(D)) and, less commonly, mutations of the ribosomal target site of macrolides. A wide array of genetic elements have emerged that facilitate macrolide resistance in S. pneumoniae; for example erm(B) is found on Tn917, while the mef (E)/mel operon is carried on the 5.4- or 5.5-kb Mega element. The macrolide resistance determinants, erm(B) and mef (E)/mel, are also found on large composite Tn916-like elements most notably Tn6002, Tn2009, and Tn2010. Introductions of 7-valent and 13-valent pneumococcal conjugate vaccines (PCV-7 and PCV-13) have decreased the incidence of macrolide-resistant invasive pneumococcal disease, but serotype replacement and emergence of macrolide resistance remain an important concern.

Screening for STIs in PrEP cohorts results in high levels of antimicrobial consumption

Abstract: Screening for STIs in men who have sex with men receiving HIV pre-exposure prophylaxis resulted in high consumption of macrolides, extended spectrum cephalosporins, fluoroquinolones and tetracyclin...