Abstract:
UNLABELLED:The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guérin (BCG), provides insufficient protection and can cause adverse events in immunocompromised individuals, such as BCGosis in HIV(+) newborns. We previously reported improved preclinical efficacy and safety of the recombinant vaccine candidate BCG ΔureC::hly, which secretes the pore-forming listeriolysin O of Listeria monocytogenes. Here, we evaluate a second-generation construct, BCG ΔureC::hly Δpdx1, which is deficient in pyridoxine synthase, an enzyme that is required for biosynthesis of the essential cofactor vitamin B6. This candidate was auxotrophic for vitamin B6 in a concentration-dependent manner, as was its survival in vivo. BCG ΔureC::hly Δpdx1 showed markedly restricted dissemination in subcutaneously vaccinated mice, which was ameliorated by dietary supplementation with vitamin B6. The construct was safer in severe combined immunodeficiency mice than the parental BCG ΔureC::hly. A prompt innate immune response to vaccination, measured by secretion of interleukin-6, granulocyte colony-stimulating factor, keratinocyte cytokine, and macrophage inflammatory protein-1α, remained independent of vitamin B6 administration, while acquired immunity, notably stimulation of antigen-specific CD4 T cells, B cells, and memory T cells, was contingent on vitamin B6 administration. The early protection provided by BCG ΔureC::hly Δpdx1 in a murine Mycobacterium tuberculosis aerosol challenge model consistently depended on vitamin B6 supplementation. Prime-boost vaccination increased protection against the canonical M. tuberculosis H37Rv laboratory strain and a clinical isolate of the Beijing/W lineage. We demonstrate that the efficacy of a profoundly attenuated recombinant BCG vaccine construct can be modulated by external administration of a small molecule. This principle fosters the development of safer vaccines required for immunocompromised individuals, notably HIV(+) infants. IMPORTANCE:Mycobacterium tuberculosis can synthesize the essential cofactor vitamin B6, while humans depend on dietary supplementation. Unlike the lipophilic vitamins A, D, and E, water-soluble vitamin B6 is well tolerated at high doses. We generated a vitamin B6 auxotroph of the phase II clinical tuberculosis vaccine candidate bacillus Calmette-Guérin ΔureC::hly. The next-generation candidate was profoundly attenuated compared to the parental strain. Adaptive immunity and protection in mice consistently depended on increased dietary vitamin B6 above the daily required dose. Control of vaccine efficacy via food supplements such as vitamin B6 could provide a fast track toward improved safety. Safer vaccines are urgently needed for HIV-infected individuals at high risk of adverse events in response to live vaccines.
journal_name
mBiojournal_title
mBioauthors
Gengenbacher M,Vogelzang A,Schuerer S,Lazar D,Kaiser P,Kaufmann SHdoi
10.1128/mBio.01262-14subject
Has Abstractpub_date
2014-06-03 00:00:00pages
e01262-14issue
3issn
2150-7511pii
mBio.01262-14journal_volume
5pub_type
杂志文章相关文献
mBio文献大全abstract:UNLABELLED:The human pathogen Streptococcus pneumoniae (pneumococcus) exhibits a high degree of genomic diversity and plasticity. Isolates with high genomic similarity are grouped into lineages that undergo homologous recombination at variable rates. PMEN1 is a pandemic, multidrug-resistant lineage. Heterologous gene e...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00173-15
更新日期:2015-06-16 00:00:00
abstract::Can accumulation of a normally transient metabolite affect fungal biology? UDP-4-keto-6-deoxyglucose (UDP-KDG) represents an intermediate stage in conversion of UDP-glucose to UDP-rhamnose. Normally, UDP-KDG is not detected in living cells, because it is quickly converted to UDP-rhamnose by the enzyme UDP-4-keto-6-deo...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01559-17
更新日期:2017-11-21 00:00:00
abstract::Antimicrobial resistance is a major health threat as it limits treatment options for infection. At the forefront of this serious issue is Acinetobacter baumannii, a Gram-negative opportunistic pathogen that exhibits the remarkable ability to resist antibiotics through multiple mechanisms. As bacterial ribosomes repres...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.03117-19
更新日期:2020-01-21 00:00:00
abstract:UNLABELLED:Toll-like receptors (TLRs) are sensors that recognize molecular patterns from viruses, bacteria, and fungi to initiate innate immune responses to invading pathogens. The emergence of highly pathogenic coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00638-15
更新日期:2015-05-26 00:00:00
abstract::Burkholderia pseudomallei, the founding member of the B. pseudomallei complex (Bpc), is a biothreat agent and causes melioidosis, a disease whose treatment mainly relies on ceftazidime and meropenem. The concern is that B. pseudomallei could enhance its drug resistance repertoire by the acquisition of DNA from resista...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00592-20
更新日期:2020-04-14 00:00:00
abstract::Lassa virus (LASV) infection is a major public health concern due to high fatality rates and limited effective treatment. The interferon-stimulated gene cholesterol 25-hydroxylase (CH25H) encodes an enzyme that catalyzes the production of 25-hydroxycholesterol (25HC). 25HC is involved in regulating cholesterol biosynt...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01808-16
更新日期:2016-12-20 00:00:00
abstract::Here, we investigate a monoclonal antibody, Z2B3, isolated from an H7N9-infected patient, that exhibited cross-reactivity to both N9 (group 2) and a broad range of seasonal and avian N1 (group 1) proteins but lost activity to the N1 with the substitution K432E. This substitution exists in 99.25% of seasonal influenza ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02315-20
更新日期:2020-10-06 00:00:00
abstract::A central question in mechanobiology is how cellular-scale structures are established and regulated. In bacteria, the cell envelope is essential for mechanical integrity, protecting against environmental stresses and bearing the load from high turgor pressures. Trivedi et al. (mBio 9:e01340-18, 2018, https://doi.org/1...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.02127-18
更新日期:2018-10-23 00:00:00
abstract::Microbes inhabit diverse environmental locations, and many species need to shift their physiology between different niches. To do this effectively requires the accurate sensing of and response to the environment. For pathogens, exposure to light is one major change between a free-living saprophyte lifestyle and causat...
journal_title:mBio
pub_type: 评论,杂志文章
doi:10.1128/mBio.00260-13
更新日期:2013-04-30 00:00:00
abstract:UNLABELLED:Cholera continues to be a global threat, with high rates of morbidity and mortality. In 2011, a cholera outbreak occurred in Palawan, Philippines, affecting more than 500 people, and 20 individuals died. Vibrio cholerae O1 was confirmed as the etiological agent. Source attribution is critical in cholera outb...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00047-15
更新日期:2015-04-21 00:00:00
abstract::New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agents in vitro All five compounds showed good activity against M. tu...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01276-18
更新日期:2018-10-09 00:00:00
abstract::Lateral gene transfer (LGT) profoundly shapes the evolution of bacterial lineages. LGT across disparate phylogenetic groups and genome content diversity between related organisms suggest a model of bacterial evolution that views LGT as rampant and promiscuous. It has even driven the argument that species concepts and ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00644-17
更新日期:2017-06-06 00:00:00
abstract:UNLABELLED:Many filamentous cyanobacteria produce specialized nitrogen-fixing cells called heterocysts, which are located at semiregular intervals along the filament with about 10 to 20 photosynthetic vegetative cells in between. Nitrogen fixation in these complex multicellular bacteria depends on metabolite exchange b...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02109-14
更新日期:2015-03-17 00:00:00
abstract:UNLABELLED:A change in viral hemagglutinin (HA) receptor binding specificity from α2,3- to α2,6-linked sialic acid is necessary for highly pathogenic avian influenza (AI) virus subtype H5N1 to become pandemic. However, details of the human-adaptive change in the H5N1 virus remain unknown. Our database search of H5N1 cl...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00081-15
更新日期:2015-04-07 00:00:00
abstract::Nicotine, a toxic and addictive alkaloid from tobacco, is an environmental pollutant in areas near cigarette production facilities. Over the last decade, our group has studied, in depth, the pyrrolidine pathway of nicotine degradation in Pseudomonas putida S16. However, little is known regarding whole mechanism(s) reg...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00602-19
更新日期:2019-06-04 00:00:00
abstract::Trauma-related necrotizing myocutaneous mucormycosis (NMM) has a high morbidity and mortality in victims of combat-related injuries, geometeorological disasters, and severe burns. Inspired by the observation that several recent clusters of NMM have been associated with extreme mechanical forces (e.g., during tornados)...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01414-20
更新日期:2020-06-30 00:00:00
abstract::Sinorhizobium meliloti is an alphaproteobacterium belonging to the Rhizobiales Bacteria from this order elongate their cell wall at the new cell pole, generated by cell division. Screening for protein interaction partners of the previously characterized polar growth factors RgsP and RgsM, we identified the inner membr...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00306-20
更新日期:2020-06-30 00:00:00
abstract:UNLABELLED:Filamentous, heterocyst-forming cyanobacteria exchange nutrients and regulators between cells for diazotrophic growth. Two alternative modes of exchange have been discussed involving transport either through the periplasm or through septal junctions linking adjacent cells. Septal junctions and channels in th...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00376-15
更新日期:2015-06-30 00:00:00
abstract:UNLABELLED:The current tuberculosis (TB) vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), provides insufficient protection against pulmonary TB. Previously, we generated a listeriolysin-expressing recombinant BCG strain, which to date has successfully completed phase I and phase IIa clinical trials. In an a...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00679-16
更新日期:2016-05-24 00:00:00
abstract::Murein lipoprotein (Lpp) and peptidoglycan-associated lipoprotein (Pal) are major outer membrane lipoproteins in Escherichia coli Their roles in cell-envelope integrity have been documented in E. coli laboratory strains, and while Lpp has been linked to serum resistance in vitro, the underlying mechanism has not been ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00603-17
更新日期:2017-05-23 00:00:00
abstract:UNLABELLED:A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal dr...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00536-15
更新日期:2015-06-02 00:00:00
abstract:UNLABELLED:Mammalian lipopolysaccharide (LPS) binding proteins (LBPs) occur mainly in extracellular fluids and promote LPS delivery to specific host cell receptors. The function of LBPs has been studied principally in the context of host defense; the possible role of LBPs in nonpathogenic host-microbe interactions has ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01193-15
更新日期:2015-10-13 00:00:00
abstract::DNA supercoiling (DS) is essential for life because it controls critical processes, including transcription, replication, and recombination. Current methods to measure DNA supercoiling in vivo are laborious and unable to examine single cells. Here, we report a method for high-throughput measurement of bacterial DNA su...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01053-20
更新日期:2020-07-28 00:00:00
abstract:UNLABELLED:The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of ...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00010-12
更新日期:2012-04-10 00:00:00
abstract::Adaptation to alternating CO2 concentrations is crucial for all organisms. Carbonic anhydrases-metalloenzymes that have been found in all domains of life-enable fixation of scarce CO2 by accelerating its conversion to bicarbonate and ensure maintenance of cellular metabolism. In fungi and other eukaryotes, the carboni...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.02211-16
更新日期:2017-01-31 00:00:00
abstract:UNLABELLED:Moraxella catarrhalis is a human respiratory pathogen that causes acute otitis media in children and is associated with exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). The first step in M. catarrhalis colonization is adherence to the mucosa, epithelial cells, and extrac...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00066-16
更新日期:2016-03-22 00:00:00
abstract::Measurements of the presence of prions in biological tissues or fluids rely more and more on cell-free assays. Although protein misfolding cyclic amplification (PMCA) has emerged as a valuable, sensitive tool, it is currently hampered by its lack of robustness and rapidity for high-throughput purposes. Here, we made a...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00829-13
更新日期:2013-12-31 00:00:00
abstract::Pathogens frequently employ eukaryotic linear motif (ELM)-rich intrinsically disordered proteins (IDPs) to perturb and hijack host cell networks for a productive infection. Mycobacterium tuberculosis has a relatively high percentage of IDPs in its proteome, the significance of which is not known. The Mycobacterium-spe...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.01712-17
更新日期:2018-01-23 00:00:00
abstract::Protein lysine acetylation, a prevalent posttranslational modification, regulates numerous crucial biological processes in cells. Nevertheless, how lysine acetylation interacts with other types of regulation to coordinate metabolism remains largely unknown owing to the complexity of the process. Here, using a represen...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00650-20
更新日期:2020-08-18 00:00:00
abstract::The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expres...
journal_title:mBio
pub_type: 杂志文章
doi:10.1128/mBio.00266-11
更新日期:2011-12-20 00:00:00