Prevalence of HIV drug resistance at antiretroviral treatment failure across regions of Russia.

BACKGROUND: This study aimed to investigate mutations associated with, the causes of, and the conditions that contribute to HIV drug resistance (DR). This research provides crucial insights into the mechanisms through which HIV evades antiretroviral drugs and suggests strategies to counter this phenomenon. Our objective was to assess the prevalence and structure of DR in HIV-1 across various regions in Russia and identify the primary factors influencing the development of HIV DR. METHODS: The study used nucleotide sequences from the HIV-1 pol gene obtained from 1369 patients with a history of therapy and virological failure between 2005 and 2019 to analyze the frequency and structure of DR and the factors associated with it. RESULTS: The analysed HIV-1 genotypes included viruses resistant to nucleoside reverse transcriptase inhibitors (NRTIs; 11.8%), non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.4%), and NRTIs + NNRTIs (31.7%). The mutations M184V/I and G190A/S/E were the most prevalent, accounting for 54.5% and 26.6%, respectively. The dominance of multiple DR persisted throughout the entire observation period. The likelihood of encountering drug-resistant variants was increased among men, patients in the late stage of infection, and those with a viral load <30 000 RNA copies/mL. Injection drug use was not associated with DR. CONCLUSION: This study has yielded new insights into HIV DR in Russia, offering valuable information to identify clinical or programmatic events warranting closer attention and support.

Stigma, serostatus disclosure, coping strategies, and the role of social capital resources among HIV care-nonadherent MSM in Russia: a qualitative analysis.

The HIV epidemic continues to expand in Russia, with suboptimal levels of care uptake. This qualitative study aimed to characterize social capital resources and lived stigma experiences, coping, and disclosure among care-nonadherent men who have sex with men (MSM) living with HIV in Russia. Twenty-five HIV-positive MSM - recruited online - completed in-depth interviews over Zoom, with data analyzed using MAXQDA software. Stigma was more likely to be encountered in interactions with persons with whom social ties were weaker such as medical providers and relatives, particularly males. Close friends - often other HIV-positive MSM and female relatives - were the most supportive and least stigmatizing. Similar persons were most often considered for HIV serostatus disclosure. Coping strategies to reduce the impact of stigma included ignoring stigmatizing experiences, seeking support from members of one's social circle, minimizing contact with stigmatizing persons, seeking new relationships with persons who are also HIV-positive, proactively reducing stigma through involvement in advocacy roles, and correcting myths and educating others about HIV infection. These findings underscore the need for interventions to assist HIV-positive MSM in building accepting social capital resources to reduce the impact of stigma and to build support within their social networks, often with other HIV-positive MSM.

Coordination of Pt(IV) by {P8W48} Macrocyclic Inorganic Cavitand: Structural, Solution, and Electrochemical Studies.

Hydrothermal reaction of a macrocyclic inorganic POM cavitand Li17(NH4)21H2[P8W48O184] with [Pt(H2O)2(OH)4] results in coordination of up to six {Pt(H2O)x(OH)4-x} fragments to the internal surface of the polyoxoanion. The product was isolated as K22(NH4)9H3[{Pt(OH)3(H2O)}6P8W48O184]·79H2O (1) and characterized by multiple techniques in the solid state (SCXRD, XRPD, XPS, FTIR, and TGA) and in solution (NMR, ESI-MS, and HPLC-ICP-AES). Electrochemical properties were studied both in solution and as components of the paste electrode. The complex shows electrocatalytic activity in water oxidation.

Sleep-related breathing disorders and cardiometabolic risk factors in pediatric kidney transplant recipients.

BACKGROUND: SRBDs have been shown to increase the risk of cardiovascular disease, which is a significant cause of mortality in kidney transplant recipients. Few studies have investigated the association between SRBDs and cardiometabolic risk factors in pediatric kidney transplant recipients. METHODS: This was a cross-sectional study of pediatric kidney transplant recipients using baseline cardiometabolic data from a previous clinical trial (NCT01007994). Parents/guardians of pediatric kidney transplant recipients filled out 22-item PSQ. A score greater than 33% was defined as a diagnosis of a SRBD. Fisher's exact test, Mann-Whitney U test, and regressions were used to determine associations. RESULTS: Among the 58 transplant recipients enrolled, 14.80% (n = 8) of participants identified as Black and 40.7% (n = 22) were male. The median age was 13 (IQR 8.25, 17) years and median number of years post-transplant for participants was 2 (IQR 1, 4). The prevalence of SRBDs was 26% (n = 14). The presence of a SRBD was associated with abnormalities in multiple cardiometabolic risk factors including total cholesterol level (ß = 23.63; 95% CI 3.58-43.67), LDL level (ß = 24.94; 95% CI 6.37-43.50), triglyceride level (ß = 54.62; 95% CI 8.74-100.50), and LVH (OR = 5.12; 95% CI 1.12-23.45) when adjusted for age, sex, and race. CONCLUSIONS: Similar to associations reported in the general pediatric and general CKD populations, SRBD is associated with increased cardiometabolic risk in pediatric kidney transplant recipients.

Mobilizing individual social capital resources for HIV care support: results of a pilot intervention in St. Petersburg, Russia.

Half of HIV-positive persons in Russia are on antiretroviral therapy (ART), and only 27% are virally suppressed. A feasibility pilot intervention to mobilize social capital resources for HIV care support was conducted in St. Petersburg. Out-of-care or ART-nonadherent HIV-positive persons (n = 24) attended a five-session intervention to increase access social capital resources (i.e., family, friends, or providers) to mobilize supports for entering care, initiating care, and adhering to ART. HIV care indicators were assessed at baseline, an immediate followup (FU-1), and 6-month followup (FU-2) points. At FU-1, participants more frequently discussed their care experiences with others, verifying the intervention's mechanism of action. Participants increased in scales of medication taking adherence (p = 0.002, FU-1; p = 0.011, FU-2), self-efficacy (p = 0.042; FU-1), and outcome expectancies (p = 0.016, FU-2). Among persons not on ART, HIV Medication Readiness scale scores increased at FU-1 (p = 0.032) but became attenuated at FU-2. Participants tended to more frequently keep care appointments (79%, baseline to 90%, FU-1, p = 0.077); to have undetectable viral load (54%, baseline to 74%, FU-2; p = 0.063); and to have fewer past-month days with delayed or incomplete medication doses (7.8, baseline to 4.2, FU-1; p = 0.084). This novel social capital intervention is promising for improving HIV care-related outcomes and warrants a full-scale evaluation.

Predictors of HIV Care Engagement, Antiretroviral Medication Adherence, and Viral Suppression Among People Living with HIV Infection in St. Petersburg, Russia.

Over 1 million HIV infections have been diagnosed in Russia, and HIV care uptake and viral suppression are very low. 241 HIV-positive individuals in St. Petersburg were enrolled through social networks, provided blood for viral load testing, and completed measures of medication-taking adherence, readiness, and self-efficacy; psychosocial well-being; and substance use. Outcomes included attending an HIV care appointment in the past 6 months, >90% ART adherence, and undetectable viral load. 26% of participants had no recent care appointment, 18% had suboptimal adherence, and 56% had detectable viral load. Alcohol use consistently predicted all adverse health outcomes. Having no recent care visit was additionally associated with being single and greater past-month drug injection frequency. Poor adherence was additionally predicted by lower medication-taking self-efficacy and lower anxiety. Detectable viral load was additionally related to younger age. Comprehensive interventions to improve HIV care in Russia must address substance abuse, anxiety, and medication-taking self-efficacy.

Barriers and Facilitators of HIV Care Engagement: Results of a Qualitative Study in St. Petersburg, Russia.

Russia has a large HIV epidemic, but medical care engagement is low. Eighty HIV-positive persons in St. Petersburg completed in-depth interviews to identify barriers and facilitators of medical HIV care engagement. The most commonly-reported barriers involved difficulties accessing care providers, dissatisfaction with the quality of services, and negative attitudes of provider staff. Other barriers included not having illness symptoms, life stresses, low value placed on health, internalized stigma and wanting to hide one's HIV status, fears of learning about one's true health status, and substance abuse. Care facilitators were feeling responsible for one's health and one's family, care-related support from other HIV-positive persons, and the onset of health decline and fear of death. Substance use remission facilitated care engagement, as did good communication from providers and trust in one's doctor. Interventions are needed in Russia to address HIV care infrastructural barriers and integrate HIV, substance abuse, care, and psychosocial services.

Dothistroma septosporum and Dothistroma pini, the causal agents of Dothistroma needle blight, are infected by multiple viruses.

Dothistroma septosporum and Dothistroma pini are severe foliar pathogens of conifers. They infect a broad spectrum of hosts (mainly Pinus spp.), causing chlorosis, defoliation of needles, and eventually the death of pine trees in extreme cases. Mycoviruses represent a novel and innovative avenue for controlling pathogens. To search for possible viruses hosted by Dothistroma spp. we screened a subset of isolates (20 strains of D. septosporum and one D. pini) originating from the Czech Republic, Slovenia, Italy, Austria and Ireland for viral dsRNA segments. Only five of them showed the presence of dsRNA segments. A total of 21 fungal isolates were prepared for total RNA extractions. RNA samples were pooled, and two separate RNA libraries were constructed for stranded total RNA sequencing. RNA-Seq data processing, pairwise sequence comparisons (PASC) and phylogenetic analyses revealed the presence of thirteen novel putative viruses with varying genome types: seven negative-sense single-stranded RNA viruses, including six bunya-like viruses and one new member of the order Mononegavirales; three positive-sense single-stranded RNA viruses, two of which are similar to those of the family Narnaviridae, while the genome of the third correspond to those of the family Gammaflexiviridae; and three double-stranded RNA viruses, comprising two novel members of the family Chrysoviridae and a potentially new species of gammapartitivirus. The results were confirmed with RT-PCR screening that the fungal pathogens hosted all the viruses and showed that particular fungal strains harbour multiple virus infections and that they are transmitted vertically. In this study, we described the narnavirus infecting D. pini. To our knowledge, this is the first virus discovered in D. pini.

Rev Protein Diversity in HIV-1 Group M Clades.

The HIV-1 Rev protein expressed in the early stage of virus replication is involved in the nuclear export of some forms of virus RNA. Naturally occurring polymorphisms in the Rev protein could influence its activity. The association between the genetic features of different virus variants and HIV infection pathogenesis has been discussed for many years. In this study, Rev diversity among HIV-1 group M clades was analyzed to note the signatures that could influence Rev activity and, subsequently, clinical characteristics. From the Los Alamos HIV Sequence Database, 4962 Rev sequences were downloaded and 26 clades in HIV-1 group M were analyzed for amino acid changes, conservation in consensus sequences, and the presence of clade-specific amino acid substitutions (CSSs) and the Wu-Kabat protein variability coefficient (WK). Subtypes G, CRF 02_AG, B, and A1 showed the largest amino acid changes and diversity. The mean conservation of the Rev protein was 80.8%. In consensus sequences, signatures that could influence Rev activity were detected. In 15 out of 26 consensus sequences, an insertion associated with the reduced export activity of the Rev protein, 95QSQGTET96, was identified. A total of 32 CSSs were found in 16 clades, wherein A6 had the 41Q substitution in the functionally significant region of Rev. The high values of WK coefficient in sites 51 and 82, located on the Rev interaction surface, indicate the susceptibility of these positions to evolutionary replacements. Thus, the noted signatures require further investigation.

Evaluation of the age-specific relationship between PTH and vitamin D metabolites.

A commonly used method for determining vitamin D sufficiency is the suppression of excess PTH secretion. Conventionally, the main circulating vitamin D metabolite 25(OH)D is used for this assessment, however, the cut-off data for this parameter vary widely in the literature. The role of other metabolites as markers of vitamin D status is actively debated. The aim of our study was to assess the relationship between PTH, age and parameters characterizing vitamin D status, both "classical" - 25(OH)D3, and "non-classical" - 24,25(OH)2D3 and 25(OH)D3/24,25(OH)2D3 (vitamin D metabolite ratio, VMR). This prospective non-controlled cohort study included 162 apparently healthy Caucasian adult volunteers. When PTH was binarized according to the median value, at VMR < 14.9, 25(OH)D3 > 9.7 ng/mL and 24,25(OH)2D3 > 0.64 ng/mL there was a pronounced relationship between PTH and age (p = 0.001, p = 0.023 and p = 0.0134 respectively), with the prevalence of higher PTH levels in older individuals and vice versa. Moreover, at an age of <40.3 years, there was a pronounced relationship between PTH and VMR (p < 0.001), and similarly at an age of <54.5 years, there was a pronounced relationship between PTH and 25(OH)D3 (p = 0.002) as well as between PTH and 24,25(OH)2D3 (p = 0.0038): in younger people, higher PTH values prevailed only in the range of vitamin D insufficiency, while in the older age group this relationship was not demonstrated and PTH values were in general above the median. VMR controlled the correlation between PTH and age more strongly than metabolites 25(OH)D3 and 24,25(OH)2D3 (p = 0.0012 vs. p > 0.05 and p = 0.0385 respectively). The optimal threshold was found equal to 11.7 for VMR such that the relationship between PTH and age in the subset of participants with VMR < 11.7 was characterized by a correlation coefficient of ρ = 0.68 (p < 0.001), while the cohort with VMR > 11.7 was characterized by a very weak correlation coefficient of ρ = 0.12 (p = 0.218), which is non-significant. In summary, our findings suggest that the relationship between PTH and vitamin D is age-dependent, with a greater susceptibility to elevated PTH among older individuals even with preserved renal function, likely due to the resistance to vitamin D function. We propose VMR can be considered as a potential marker of vitamin D status. These findings require confirmation in larger population-based studies.

OCTDL: Optical Coherence Tomography Dataset for Image-Based Deep Learning Methods.

Optical coherence tomography (OCT) is a non-invasive imaging technique with extensive clinical applications in ophthalmology. OCT enables the visualization of the retinal layers, playing a vital role in the early detection and monitoring of retinal diseases. OCT uses the principle of light wave interference to create detailed images of the retinal microstructures, making it a valuable tool for diagnosing ocular conditions. This work presents an open-access OCT dataset (OCTDL) comprising over 2000 OCT images labeled according to disease group and retinal pathology. The dataset consists of OCT records of patients with Age-related Macular Degeneration (AMD), Diabetic Macular Edema (DME), Epiretinal Membrane (ERM), Retinal Artery Occlusion (RAO), Retinal Vein Occlusion (RVO), and Vitreomacular Interface Disease (VID). The images were acquired with an Optovue Avanti RTVue XR using raster scanning protocols with dynamic scan length and image resolution. Each retinal b-scan was acquired by centering on the fovea and interpreted and cataloged by an experienced retinal specialist. In this work, we applied Deep Learning classification techniques to this new open-access dataset.

Identification of the novel HLA-C*02:212 allele detected in a potential hematopoietic stem cell donor.

The novel HLA-C*02:212 allele was characterized using next generation sequencing technology.

Recombinant Forms of HIV-1 in the Last Decade of the Epidemic in the Russian Federation.

Currently, HIV-1 displays a substantial level of genetic diversity on a global scale, partly attributed to its recombinant variants. This study seeks to identify and analyze HIV-1 recombinants in Russia during the last decade of the epidemic. A comprehensive examination was conducted, encompassing 3178 partial pol sequences. Subtyping was achieved through various programs including COMET, the Stanford Database, REGA, jpHMM, RIP, and RDP4 for recombination analysis. The study also involved phylogenetic analysis to trace the origins of the identified recombinants. Primary resistance (PrimDR) prevalence and Drug Resistance Mutations (DRMs) were assessed. The study uncovered an overall proportion of recombinants at 8.7%, with a statistically significant increase in their frequency observed over time (p < 0.001). The Northwestern (18.5%) and Siberian (15.0%) Federal Districts exhibited a high prevalence of recombinants, while the Volga (1.9%) and Ural (2.8%) Federal Districts had a lower prevalence. Among HIV-1 recombinants, a PrimDR prevalence of 11.4% was identified. Notably, significant differences in DRMs were observed, with a higher prevalence of M184V in sub-subtype A6 (p = 0.018) and K103N in CRF63_02A6 (p = 0.002). These findings underscore the increasing HIV-1 genetic diversity and highlight a substantial prevalence of PrimDR among its recombinant forms, emphasizing the necessity for ongoing systematic monitoring.

Current Trends of HIV Infection in the Russian Federation.

Russia remains one of the areas most affected by HIV in Eastern Europe and Central Asia. The aim of this study was to analyze HIV infection indicators and study trends in Russia using data from the Federal Statistic Form No. 61 "Information about HIV infection". HIV incidence, prevalence, HIV testing and mortality rates (from 2011 to 2022), and treatment success rates (from 2016 to 2022) were analyzed. These indicators were compared across different federal districts (FDs) of Russia. The findings revealed a significant downward trend in HIV incidence, while a significant upward trend was observed for HIV prevalence. The mortality rate has stabilized since 2018. The coverage of HIV testing and antiretroviral therapy increased over time. The number of people living with HIV-1 (PLWH) with a suppressed viral load in Russia as a whole varied between 72% and 77% during the years under observation. The Siberian and Ural federal districts recorded the highest HIV incidence, while the North Caucasian FD reported the lowest. An increase in HIV testing coverage was observed across all FDs. This comprehensive evaluation of HIV infection indicators within the regional context contributes to the timely implementation of measures aimed at preventing the spread of HIV.

Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.

Tat, the trans-activator of transcription, is a multifunctional HIV-1 protein that can induce chronic inflammation and the development of somatic diseases in HIV-infected patients. Natural polymorphisms in Tat can impact the propagation of the inflammatory signal. Currently, Tat is considered an object for creating new therapeutic agents. Therefore, the identification of Tat protein features in various HIV-1 variants is a relevant task. The purpose of the study was to characterize the genetic variations of Tat-A6 in virus variants circulating in the Moscow Region. The authors analyzed 252 clinical samples from people living with HIV (PLWH) with different stages of HIV infection. Nested PCR for two fragments (tat1, tat2) with subsequent sequencing, subtyping, and statistical analysis was conducted. The authors received 252 sequences for tat1 and 189 for tat2. HIV-1 sub-subtype A6 was identified in 250 samples. The received results indicated the features of Tat1-A6 in variants of viruses circulating in the Moscow Region. In PLWH with different stages of HIV infection, C31S in Tat1-A6 was detected with different occurrence rates. It was demonstrated that Tat2-A6, instead of a functional significant 78RGD80 motif, had a 78QRD80 motif. Herewith, G79R in Tat2-A6 was defined as characteristic amino acid substitution for sub-subtype A6. Tat2-A6 in variants of viruses circulating in the Moscow Region demonstrated high conservatism.

HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006-2022.

In Russia, antiretroviral therapy (ART) coverage has significantly increased, which, in the absence of routine genotyping testing, could lead to an increase in HIV drug resistance (DR). The aim of this study was to investigate the patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database (4481 protease and reverse transcriptase and 844 integrase gene sequences). HIV genetic variants, and DR and DR mutations (DRMs) were determined using the Stanford Database. The analysis showed high viral diversity, with the predominance of A6 (78.4%), which was the most common in all transmission risk groups. The overall prevalence of surveillance DRMs (SDRMs) was 5.4%, and it reached 10.0% in 2022. Most patients harbored NNRTI SDRMs (3.3%). The prevalence of SDRMs was highest in the Ural (7.9%). Male gender and the CRF63_02A6 variant were association factors with SDRMs. The overall prevalence of DR was 12.7% and increased over time, primarily due to NNRTIs. Because baseline HIV genotyping is unavailable in Russia, it is necessary to conduct surveillance of HIV DR due to the increased ART coverage and DR prevalence. Centralized collection and unified analysis of all received genotypes in the national database can help in understanding the patterns and trends in DR to improve treatment protocols and increase the effectiveness of ART. Moreover, using the national database can help identify regions or transmission risk groups with a high prevalence of HIV DR for epidemiological measures to prevent the spread of HIV DR in the country.

Post-Vaccination and Post-Infection Immunity to the Hepatitis B Virus and Circulation of Immune-Escape Variants in the Russian Federation 20 Years after the Start of Mass Vaccination.

A neonatal vaccination against the Hepatitis B virus (HBV) infection was initiated in Russia 20 years ago, with catch-up immunization for adolescents and adults under the age of 60 years launched in 2006. Here, we have assessed the humoral immunity to HBV in different regions of Russia, as well as the infection frequency following 20 years of a nationwide vaccination campaign. We have also evaluated the role of immune-escape variants in continuing HBV circulation. A total of 36,149 healthy volunteers from nine regions spanning the Russian Federation from west to east were tested for HBV surface antigen (HBsAg), antibodies to HBV capsid protein (anti-HBc), and antibodies to HBsAg (anti-HBs). HBV sequences from 481 chronic Hepatitis B patients collected from 2018-2022 were analyzed for HBsAg immune-escape variants, compared with 205 sequences obtained prior to 2010. Overall, the HBsAg detection rate was 0.8%, with this level significantly exceeded only in one study region, the Republic of Dagestan (2.4%, p < 0.0001). Among the generation vaccinated at birth, the average HBsAg detection rate was below 0.3%, ranging from 0% to 0.7% depending on the region. The anti-HBc detection rate in subjects under 20 years was 7.4%, indicating ongoing HBV circulation. The overall proportion of participants under 20 years with vaccine-induced HBV immunity (anti-HBs positive, anti-HBc negative) was 41.7% but below 10% in the Tuva Republic and below 25% in the Sverdlovsk and Kaliningrad regions. The overall prevalence of immune-escape HBsAg variants was 25.2% in sequences obtained from 2018-2022, similar to the prevalence of 25.8% in sequences collected prior to 2010 (p > 0.05). The population dynamics of immune-escape variants predicted by Bayesian analysis have remained stable over the last 20 years, indicating the absence of vaccine-driven positive selection. In contrast, the wild-type HBV population size experienced a rapid decrease starting in the mid-1990s, following the introduction of mass immunization, but it subsequently began to recover, reaching pre-vaccination levels by 2020. Taken together, these data indicate that it is gaps in vaccination, and not virus evolution, that may be responsible for the continued virus circulation despite 20 years of mass vaccination.

Draft Genome Sequences of Three Streptomycetes Isolated from Frobisher Bay Marine Sediments.

Three Streptomyces strains (RKAG290, RKAG293, and RKAG337) were isolated from intertidal marine sediments of Frobisher Bay (Canada).

Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients.

General consensus suggests that even singleton E138A mutations in HIV reverse transcriptase at baseline are associated with resistance to rilpivirine (RPV). We detected 11 pre-existing E138A carriers treated with RPV in the pan European EuResist database. However, all 11 patients presented with full virological efficacy for first-line RPV-based ART regimens.

Revealing a New Family of D-2-Hydroxyglutarate Dehydrogenases in Escherichia coli and Pantoea ananatis Encoded by ydiJ.

In E. coli and P. ananatis, L-serine biosynthesis is initiated by the action of D-3-phosphoglycerate dehydrogenase (SerA), which converts D-3-phosphoglycerate into 3-phosphohydroxypyruvate. SerA can concomitantly catalyze the production of D-2-hydroxyglutarate (D-2-HGA) from 2-ketoglutarate by oxidizing NADH to NAD+. Several bacterial D-2-hydroxyglutarate dehydrogenases (D2HGDHs) have recently been identified, which convert D-2-HGA back to 2-ketoglutarate. However, knowledge about the enzymes that can metabolize D-2-HGA is lacking in bacteria belonging to the Enterobacteriaceae family. We found that ydiJ encodes novel D2HGDHs in P. ananatis and E. coli, which were assigned as D2HGDHPa and D2HGDHEc, respectively. Inactivation of ydiJ in P. ananatis and E. coli led to the significant accumulation of D-2-HGA. Recombinant D2HGDHEc and D2HGDHPa were purified to homogeneity and characterized. D2HGDHEc and D2HGDHPa are homotetrameric with a subunit molecular mass of 110 kDa. The pH optimum was 7.5 for D2HGDHPa and 8.0 for D2HGDHEc. The Km for D-2-HGA was 208 µM for D2HGDHPa and 83 µM for D2HGDHEc. The enzymes have strict substrate specificity towards D-2-HGA and displayed maximal activity at 45 °C. Their activity was completely inhibited by 0.5 mM Mn2+, Ni2+ or Co2+. The discovery of a novel family of D2HGDHs may provide fundamental information for the metabolic engineering of microbial chassis with desired properties.