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Objective: Immunotherapy using vitamin D (vitD3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB).Methods: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D3 concentrations.Results: Most subjects had low baseline plasma 25(OH)D3 levels that increased gradually in the vitD3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L-1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD3 + PBA group (12.6%).Conclusion: Daily supplementation with vitD3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum. [ABSTRACT FROM AUTHOR]

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR., Competing Interests: Declaration of interests SBe, ZD, CMC, HHB, NG, MH-A, BA, HS, TW, BDH, and VI are WHO employees. KVW and ACa were WHO employees. KUK and SBu are WHO consultants. ACh, DD, RLH, and IDO were WHO consultants. RLH is also supported by the Wellcome Trust (106680/Z/14/Z). All authors declare no other competing interests. Declarations of competing interests of the collaborators for the WHO research agenda for AMR in human health were reviewed and are available upon request to the corresponding author., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Most individuals developing tuberculosis (TB) are working age adults living in low- and middle-income countries (LMICs). The resulting disability and death impact economic productivity and burden health systems. New TB vaccine products may reduce this burden. In this study, we estimated the impact of introducing novel TB vaccines on gross domestic product (GDP) growth in 105 LMICs., Methods and Findings: We adapted an existing macroeconomic model to simulate country-level GDP trends between 2020 and 2080, comparing scenarios for introduction of hypothetical infant and adolescent/adult vaccines to a no-new-vaccine counterfactual. We parameterized each scenario using estimates of TB-related mortality, morbidity, and healthcare spending from linked epidemiological and costing models. We assumed vaccines would be introduced between 2028 and 2047 and estimated incremental changes in GDP within each country from introduction to 2080, in 2020 US dollars. We tested the robustness of results to alternative analytic specifications. Both vaccine scenarios produced greater cumulative GDP in the modeled countries over the study period, equivalent to $1.6 (95% uncertainty interval: $0.8, 3.0) trillion for the adolescent/adult vaccine and $0.2 ($0.1, 0.4) trillion for the infant vaccine. These GDP gains were substantially lagged relative to the time of vaccine introduction, particularly for the infant vaccine. GDP gains resulting from vaccine introduction were concentrated in countries with higher current TB incidence and earlier vaccine introduction. Results were sensitive to secular trends in GDP growth but relatively robust to other analytic assumptions. Uncertain projections of GDP could alter these projections and affect the conclusions drawn by this analysis., Conclusions: Under a range of assumptions, introducing novel TB vaccines would increase economic growth in LMICs., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Members of the funder (EP, NG, MZ) participated as authors on the study and critically reviewed the analysis, reviewed and revised the manuscript, and approved the final manuscript as submitted. All other authors have declared that no competing interests exist., (Copyright: © 2023 Portnoy et al. This is an open access article distributed under the Creative Commons Attribution IGO License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/3.0/igo/. In any use of this article, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.)

Introduction: One in two patients developing tuberculosis (TB) in low-income and middle-income countries (LMICs) faces catastrophic household costs. We assessed the potential financial risk protection from introducing novel TB vaccines, and how health and economic benefits would be distributed across income quintiles., Methods: We modelled the impact of introducing TB vaccines meeting the World Health Organization preferred product characteristics in 105 LMICs. For each country, we assessed the distribution of health gains, patient costs and household financial vulnerability following introduction of an infant vaccine and separately for an adolescent/adult vaccine, compared with a 'no-new-vaccine' counterfactual. Patient-incurred direct and indirect costs of TB disease exceeding 20% of annual household income were defined as catastrophic., Results: Over 2028-2050, the health gains resulting from vaccine introduction were greatest in lower income quintiles, with the poorest 2 quintiles in each country accounting for 56% of total LMIC TB cases averted. Over this period, the infant vaccine was estimated to avert US$5.9 (95% uncertainty interval: US$5.3-6.5) billion in patient-incurred total costs, and the adolescent/adult vaccine was estimated to avert US$38.9 (US$36.6-41.5) billion. Additionally, 3.7 (3.3-4.1) million fewer households were projected to face catastrophic costs with the infant vaccine and 22.9 (21.4-24.5) million with the adolescent/adult vaccine, with 66% of gains accruing in the poorest 2 income quintiles., Conclusion: Under a range of assumptions, introducing novel TB vaccines would reduce income-based inequalities in the health and household economic outcomes of TB in LMICs., Competing Interests: Competing interests: RAC is funded by BMGF (INV-001754) and received a grant from the Canadian Centennial Scholarship Fund. CKW is funded by UKRI/MRC (MR/N013638/1). RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754) and the WHO (2020/985800-0). Members of the funder participated as authors on the study. All other authors declare no conflicts of interest., (© World Health Organization 2023. Licensee BMJ.)

Background: Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks resulting from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low-income and middle-income countries (LMICs) in several delivery scenarios., Methods: We calibrated a tuberculosis model to 105 LMICs (accounting for 93% of global incidence). Vaccine scenarios were implemented as the base-case (routine vaccination of those aged 9 years and one-off vaccination for those aged 10 years and older, with country-specific introduction between 2028 and 2047, and 5-year scale-up to target coverage); accelerated scale-up similar to the base-case, but with all countries introducing vaccines in 2025, with instant scale-up; and routine-only (similar to the base-case, but including routine vaccination only). Vaccines were assumed to protect against disease for 10 years, with 50% efficacy., Findings: The base-case scenario would prevent 44·0 million (95% uncertainty range 37·2-51·6) tuberculosis cases and 5·0 million (4·6-5·4) tuberculosis deaths before 2050, compared with equivalent estimates of cases and deaths that would be predicted to occur before 2050 with no new vaccine introduction (the baseline scenario). The accelerated scale-up scenario would prevent 65·5 million (55·6-76·0) cases and 7·9 million (7·3-8·5) deaths before 2050, relative to baseline. The routine-only scenario would prevent 8·8 million (95% uncertainty range 7·6-10·1) cases and 1·1 million (0·9-1·2) deaths before 2050, relative to baseline., Interpretation: Our results suggest novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a one-off vaccination campaign will be crucial for rapid impact. Accelerated introduction-at a pace similar to that seen for COVID-19 vaccines-would increase the number of lives saved before 2050 by around 60%. Investment is required to support vaccine development, manufacturing, prompt introduction, and scale-up., Funding: WHO (2020/985800-0)., Translations: For the French, Spanish, Italian and Dutch translations of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests SM reports employment by the International AIDS Vaccine Initiative, a non-profit product development partnership supporting the access-oriented development of vaccines for several disease areas, including tuberculosis, and grant funding from WHO. MJ is funded by the Bill & Melinda Gates Foundation, Gavi the Vaccine Alliance, the UK Research Institute, the National Institute for Health Research, the European Commission, and the Wellcome Trust, and reports leadership or fiduciary roles in the board, society, committee, or advocacy groups for WHO and Gavi. RCH reports employment by Sanofi Pasteur, unrelated to tuberculosis and outside the submitted work. NAM received consulting fees from The Global Fund to Fight AIDS, Tuberculosis and Malaria and WHO, and reports funding to their institution from the US Centers for Disease Control and Prevention, the Gates Foundation, the National Institute of Health, and the US Council of State and Territorial Epidemiologists. RGW is funded for other work by the Wellcome Trust (218261/Z/19/Z), the National Institute of Health (1R01AI147321–01), EDCTP (RIA208D-2505B), the UK's Medical Research Council (CCF17–7779 via SET Bloomsbury), the Economic and Social Research Council (ES/P008011/1), the Gates Foundation (OPP1084276, OPP1135288, and INV-001754), and WHO. All other authors declare no competing interests., (Copyright © 2023 World Health Organization; licensee Elsevier. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Tuberculosis (TB) is preventable and curable but eliminating it has proven challenging. Safe and effective TB vaccines that can rapidly reduce disease burden are essential for achieving TB elimination. We assessed future costs, cost-savings, and cost-effectiveness of introducing novel TB vaccines in low- and middle-income countries (LMICs) for a range of product characteristics and delivery strategies., Methods and Findings: We developed a system of epidemiological and economic models, calibrated to demographic, epidemiological, and health service data in 105 LMICs. For each country, we assessed the likely future course of TB-related outcomes under several vaccine introduction scenarios, compared to a "no-new-vaccine" counterfactual. Vaccine scenarios considered 2 vaccine product profiles (1 targeted at infants, 1 at adolescents/adults), both assumed to prevent progression to active TB. Key economic inputs were derived from the Global Health Cost Consortium, World Health Organization (WHO) patient cost surveys, and the published literature. We estimated the incremental impact of vaccine introduction for a range of health and economic outcomes. In the base-case, we assumed a vaccine price of $4.60 and used a 1× per-capita gross domestic product (GDP) cost-effectiveness threshold (both varied in sensitivity analyses). Vaccine introduction was estimated to require substantial near-term resources, offset by future cost-savings from averted TB burden. From a health system perspective, adolescent/adult vaccination was cost-effective in 64 of 105 LMICs. From a societal perspective (including productivity gains and averted patient costs), adolescent/adult vaccination was projected to be cost-effective in 73 of 105 LMICs and cost-saving in 58 of 105 LMICs, including 96% of countries with higher TB burden. When considering the monetized value of health gains, we estimated that introduction of an adolescent/adult vaccine could produce $283 to 474 billion in economic benefits by 2050. Limited data availability required assumptions and extrapolations that may omit important country-level heterogeneity in epidemiology and costs., Conclusions: TB vaccination would be highly impactful and cost-effective in most LMICs. Further efforts are needed for future development, adoption, and implementation of novel TB vaccines., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Members of the funder (NG, MZ, SYS, RH, IGB, NN) participated as authors on the study and critically reviewed the analysis, reviewed and revised the manuscript, and approved the final manuscript as submitted. All other authors have declared that no competing interests exist., (Copyright: © 2023 Portnoy et al. This is an open access article distributed under the Creative Commons Attribution IGO License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/3.0/igo/. In any use of this article, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article’s original URL.)

Objective: Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO)., Study Design: We used a mixed-methods study design to develop a framework for recommendation mapping with seven key methodological considerations. We define a recommendation map as an online repository of recommendations from several guidelines on a condition, providing links to the underlying evidence and expert judgments that inform them, allowing users to filter and cross-tabulate the search results. We engaged guideline developers, users, and health software engineers in an iterative process to elaborate the WHO eTB recommendation map., Results: Applying the seven-step framework, we included 228 recommendations, linked to 103 guideline questions and organized the recommendation map according to key components of the health question, including the original recommendations and rationale (https://who.tuberculosis.recmap.org/)., Conclusion: The recommendation mapping framework provides the entire continuum of evidence mapping by framing recommendations within a guideline questions' population, interventions, and comparators domains. Recommendation maps should allow guideline developers to organize their work meaningfully, standardize the automated publication of guidelines through links to the GRADEpro guideline development tool, and increase their accessibility and usability., (Copyright © 2021. Published by Elsevier Inc.)

Dysbiosis and a dysregulated gut immune barrier function contributes to chronic immune activation in HIV-1 infection. We investigated if nutritional supplementation with vitamin D and phenylbutyrate could improve gut-derived inflammation, selected microbial metabolites, and composition of the gut microbiota. Treatment-naïve HIV-1-infected individuals ( n = 167) were included from a double-blind, randomized, and placebo-controlled trial of daily 5000 IU vitamin D and 500 mg phenylbutyrate for 16 weeks (Clinicaltrials.gov NCT01702974). Baseline and per-protocol plasma samples at week 16 were analysed for soluble CD14, the antimicrobial peptide LL-37, kynurenine/tryptophan-ratio, TMAO, choline, and betaine. Assessment of the gut microbiota involved 16S rRNA gene sequencing of colonic biopsies. Vitamin D + phenylbutyrate treatment significantly increased 25-hydroxyvitamin D levels ( p < 0.001) but had no effects on sCD14, the kynurenine/tryptophan-ratio, TMAO, or choline levels. Subgroup-analyses of vitamin D insufficient subjects demonstrated a significant increase of LL-37 in the treatment group ( p = 0.02), whereas treatment failed to significantly impact LL-37-levels in multiple regression analysis. Further, no effects on the microbiota was found in number of operational taxonomic units ( p = 0.71), Shannon microbial diversity index ( p = 0.82), or in principal component analyses ( p = 0.83). Nutritional supplementation with vitamin D + phenylbutyrate did not modulate gut-derived inflammatory markers or microbial composition in treatment-naïve HIV-1 individuals with active viral replication.

Poor nutritional status is common among human immunodeficiency virus (HIV)-infected patients including vitamin D (vitD₃) deficiency. We conducted a double-blinded, randomized, and placebo-controlled trial in Addis Ababa, Ethiopia, to investigate if daily nutritional supplementation with vitD₃ (5000 IU) and phenylbutyrate (PBA, 2 × 500 mg) could mediate beneficial effects in treatment-naïve HIV patients. Primary endpoint: the change in plasma HIV-1 comparing week 0 to 16 using modified intention-to-treat (mITT, n = 197) and per-protocol ( n = 173) analyses. Secondary endpoints: longitudinal HIV viral load, T cell counts, body mass index (BMI), middle-upper-arm circumference (MUAC), and 25(OH)D₃ levels in plasma. Baseline characteristics were detectable viral loads (median 7897 copies/mL), low CD4⁺ (median 410 cells/µL), and elevated CD8⁺ (median 930 cells/µL) T cell counts. Most subjects were vitD₃ deficient at enrolment, but a gradual and significant improvement of vitD₃ status was demonstrated in the vitD₃ + PBA group compared with placebo ( p < 0.0001) from week 0 to 16 (median 37.5 versus 115.5 nmol/L). No significant changes in HIV viral load, CD4⁺ or CD8⁺ T cell counts, BMI or MUAC could be detected. Clinical adverse events were similar in both groups. Daily vitD₃ + PBA for 16 weeks was well-tolerated and effectively improved vitD₃ status but did not reduce viral load, restore peripheral T cell counts or improve BMI or MUAC in HIV patients with slow progressive disease. Clinicaltrials.gov NCT01702974.

Objective: Immunotherapy using vitamin D (vitD 3 ) and phenylbutyrate (PBA) may support standard drug regimens used to treat infectious diseases. We investigated if vitD 3 + PBA enhanced clinical recovery from pulmonary tuberculosis (TB)., Methods: A randomized controlled trial was conducted in Addis Ababa, Ethiopia. Patients with smear-positive or smear-negative TB received daily oral supplementation with 5000 IU vitD 3 and 2 × 500 mg PBA or placebo for 16 weeks, together with 6-month chemotherapy. Primary end-point: reduction of a clinical composite TB score at week 8 compared with baseline using modified intention-to-treat (mITT, n = 348) and per-protocol (n = 296) analyses. Secondary end-points: primary and modified TB scores (week 0, 4, 8, 16, 24), sputum conversion, radiological findings and plasma 25(OH)D 3 concentrations., Results: Most subjects had low baseline plasma 25(OH)D 3 levels that increased gradually in the vitD 3 + PBA group compared with placebo (P < 0.0001) from week 0 to 16 (mean 34.7 vs. 127.4 nmol L -1 ). In the adjusted mITT analysis, the primary TB score was significantly reduced in the intervention group at week 8 (-0.52, 95% CI -0.93, -0.10; P = 0.015) while the modified TB score was reduced at week 8 (-0.58, 95% CI -1.02, -0.14; P = 0.01) and 16 (-0.34, 95% CI -0.64, -0.03; P = 0.03). VitD 3 + PBA had no effect on longitudinal sputum-smear conversion (P = 0.98). Clinical adverse events were more common in the placebo group (24.3%) compared with the vitD 3 + PBA group (12.6%)., Conclusion: Daily supplementation with vitD 3 + PBA may ameliorate clinical TB symptoms and disease-specific complications, while the intervention had no effect on bacterial clearance in sputum., (© 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Pillar 3 of the End TB Strategy calls for the promotion of research and innovation at the country level to facilitate improved implementation of existing and novel interventions to end tuberculosis (TB). In an era of increasing cross-border migration, there is a specific need to integrate migration-related issues into national TB research agendas. The objective of the present review is to provide a conceptual framework to guide countries in the development and operationalization of a migrant-inclusive TB research agenda., Methods: We conducted a literature review, complemented by expert opinion and the previous articles in this State of the Art series, to identify important themes central to migration-related TB. We categorized these themes into a framework for a migration-inclusive global TB research agenda across a comprehensive spectrum of research. We developed this conceptual framework taking into account: 1) the biomedical, social and structural determinants of TB; 2) the epidemiologic impact of the migration pathway; and 3) the feasibility of various types of research based on a country's capacity., Discussion: The conceptual framework presented here is based on the key principle that migrants are not inherently different from other populations in terms of susceptibility to known TB determinants, but that they often have exacerbated or additional risks related to their country of origin and the migration process, which must be accounted for in developing comprehensive TB prevention and care strategies. A migrant-inclusive research agenda should systematically consider this wider context to have the highest impact.

Background: Tuberculosis (TB) research is a key component of the End TB Strategy. To track research output, we conducted a bibliometric analysis of TB research from the past decade., Methods: The Web of Science database was searched for publications from January 2007 to December 2016 with "tuberculosis" in the title. References were analysed using the R bibliometrix package. A year-stratified 5% random subset was drawn to extract funding sources and identify research areas., Findings: The annual growth rate of publications was 7.3%, and was highest (13.1%) among Brazil, Russia, India, China and South Africa (BRICS). The USA was the most productive country, with 18.4% of references, followed by India (9.7%), China (7.3%), England (6.5%), and South Africa (3.9%). In the subset analysis, the most common research area was 'fundamental research' (33.8%). Frequently acknowledged funders were US and EU-based, with China and India emerging as top funders. Collaborations appeared more frequently between high-income countries and low/medium income countries (LMICs), with fewer collaborations among LMICs., Conclusion: The past decade has seen a continued increase in TB publications. While USA continues to dominate research output and funding, BRICS countries have emerged as major research producers and funders. Collaborations among BRICS would enhance future TB research productivity., Competing Interests: MP serves as a consultant to the Bill & Melinda Gates Foundation (BMGF), which had no involvement in this study or manuscript. MP serves on the Editorial Boards of PLOS Medicine & PLOS ONE. He is also a joint editor of the PLoS Tuberculosis Channel. This does not alter our adherence to PLOS ONE policies on sharing data and materials. None of the other authors have any competing interests to disclose.

Lactic acid bacteria (LAB) and yeasts were enumerated and identified from naturally fermented buttermilk. Isolates were first subjected to chemical tests and then to molecular characterization. Molecular identification involved pure sequencing of 16s rRNA (LAB) and 18s rRNA (yeast) genes. Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (DGGE) was used for detection of microbiota composition. Eighty-five LAB and 26 yeast isolates obtained from 16 small-scale dairy farms were isolated and identified. The microbial composition was dominated by strains of Lactococcus lactis ssp. lactis, Lactobacillus plantarum and Saccharomyces cerevisiae. Molecular techniques enabled not only genetic confirmation but also detection of some uncultivated strains. The presence of diverse strains of LAB and yeasts in NFB indicated a potential for development of different starter cultures to make new dairy products.

We engineered a fatty acid overproducing Escherichia coli strain through overexpressing tesA (“pull”) and fadR (“push”) and knocking out fadE (“block”). This “pull-push-block” strategy yielded 0.17 g of fatty acids (C12–C18) per gram of glucose (equivalent to 48% of the maximum theoretical yield) in batch cultures during the exponential growth phase under aerobic conditions. Metabolic fluxes were determined for the engineered E. coli and its control strain using tracer ([1,2-13C]glucose) experiments and 13C-metabolic flux analysis. Cofactor (NADPH) and energy (ATP) balances were also investigated for both strains based on estimated fluxes. Compared to the control strain, fatty acid overproduction led to significant metabolic responses in the central metabolism: (1) Acetic acid secretion flux decreased 10-fold; (2) Pentose phosphate pathway and Entner–Doudoroff pathway fluxes increased 1.5- and 2.0-fold, respectively; (3) Biomass synthesis flux was reduced 1.9-fold; (4) Anaplerotic phosphoenolpyruvate carboxylation flux decreased 1.7-fold; (5) Transhydrogenation flux converting NADH to NADPH increased by 1.7-fold. Real-time quantitative RT-PCR analysis revealed the engineered strain increased the transcription levels of pntA (encoding the membrane-bound transhydrogenase) by 2.1-fold and udhA (encoding the soluble transhydrogenase) by 1.4-fold, which is in agreement with the increased transhydrogenation flux. Cofactor and energy balances analyses showed that the fatty acid overproducing E. coli consumed significantly higher cellular maintenance energy than the control strain. We discussed the strategies to future strain development and process improvements for fatty acid production in E. coli.