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Luiz Pedro S. de Carvalho
Francis Crick Institute
EnzymeChemistryMycobacterium tuberculosisBiochemistryBiology
70Publications
25H-index
2,341Citations
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Publications 72
Newest
#1Agnese Serafini (Francis Crick Institute)H-Index: 3
#2Lendl Tan (UQ: University of Queensland)H-Index: 5
Last. Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 2
view all 17 authors...
Bacterial nutrition is an essential aspect of host–pathogen interaction. For the intracellular pathogen Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans, fatty acids derived from lipid droplets are considered the major carbon source. However, many other soluble nutrients are available inside host cells and may be used as alternative carbon sources. Lactate and pyruvate are abundant in human cells and fluids, particularly during inflammation. In this work, we study ...
6 CitationsSource
#1Dimitrios Evangelopoulos (Francis Crick Institute)H-Index: 3
#2Gareth A. Prosser (University of Manchester)H-Index: 1
Last. Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 2
view all 9 authors...
Drug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for six decades without significant appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We therefore investigated why Mycobacterium tuberculosis fails to become resistant to D-cycloserine. To address this question, we employed a combination of bacterial genetics, genomics, bioche...
4 CitationsSource
#1Hua Wang (Francis Crick Institute)H-Index: 1
#1Hua Wang (Francis Crick Institute)H-Index: 3
Last. Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 25
view all 10 authors...
Mycobacterium tuberculosis (Mtb) is the etiological agent of tuberculosis. One-fourth of the global population is estimated to be infected with Mtb, accounting for ∼1.3 million deaths in 2017. As part of the immune response to Mtb infection, macrophages produce metabolites with the purpose of inhibiting or killing the bacterial cell. Itaconate is an abundant host metabolite thought to be both an antimicrobial agent and a modulator of the host inflammatory response. However, the exact mode of act...
4 CitationsSource
#1Safaa M. Kishk (Cardiff University)H-Index: 2
#1Safaa M. Kishk (Cardiff University)H-Index: 1
Last. Claire Simons (Cardiff University)H-Index: 21
view all 13 authors...
The emergence of untreatable drug‐resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through t...
3 CitationsSource
#1Yoshikazu Kawai (Newcastle University)H-Index: 15
#2Romain Mercier (AMU: Aix-Marseille University)H-Index: 13
Last. Jeff Errington (Newcastle University)H-Index: 62
view all 6 authors...
The peptidoglycan cell wall is an essential structure for the growth of most bacteria. However, many are capable of switching into a wall-deficient L-form state in which they are resistant to antibiotics that target cell wall synthesis under osmoprotective conditions, including host environments. L-form cells may have an important role in chronic or recurrent infections. The cellular pathways involved in switching to and from the L-form state remain poorly understood. This work shows that the la...
7 CitationsSource
#1Safaa M. Kishk (Cardiff University)H-Index: 2
#1Safaa M. Kishk (Cardiff University)H-Index: 1
Last. Claire Simons (Cardiff University)H-Index: 21
view all 10 authors...
Abstract The rise in multidrug resistant (MDR) cases of tuberculosis (TB) has led to the need for the development of TB drugs with different mechanisms of action. The genome sequence of Mycobacterium tuberculosis ( Mtb ) revealed twenty different genes coding for cytochrome P450s. CYP121A1 catalyzes a C C crosslinking reaction of dicyclotyrosine (cYY) producing mycocyclosin and current research suggests that either mycocyclosin is essential or the overproduction of cYY is toxic to Mtb . A series...
3 CitationsSource
#1Samantha L. van der Beek (UU: Utrecht University)H-Index: 3
#2Azul Zorzoli (Dund.: University of Dundee)H-Index: 2
Last. Nina M. van Sorge (UU: Utrecht University)H-Index: 22
view all 11 authors...
Biosynthesis of the nucleotide sugar precursor dTDP-L-rhamnose is critical for the viability and virulence of many human pathogenic bacteria, including Streptococcus pyogenes (Group A Streptococcus; GAS), Streptococcus mutans and Mycobacterium tuberculosis. Streptococcal pathogens require dTDP-L-rhamnose for the production of structurally similar rhamnose polysaccharides in their cell wall. Via heterologous expression in S. mutans, we confirmed that GAS RmlB and RmlC are critical for dTDP-L-rham...
6 CitationsSource
#1Stephanie R. Lovell-Read (University of Oxford)H-Index: 1
#2Luiz Pedro S. de Carvalho (Francis Crick Institute)H-Index: 2
: In this issue of JEM, Reinink et al. (https://doi.org/10.1084/jem.20181812) use comparative lipidomics to identify a new family of trehalose-containing cell wall lipids that are enriched in virulent Salmonella serovars. These lipids are structurally related to the important mycobacterial immunogen cord factor.
2 CitationsSource
#1Diana FreireH-Index: 4
#2Claude Gutierrez (University of Toulouse)H-Index: 9
Last. Olivier Neyrolles (University of Toulouse)H-Index: 42
view all 23 authors...
Summary Toxin-antitoxin (TA) systems regulate fundamental cellular processes in bacteria and represent potential therapeutic targets. We report a new RES-Xre TA system in multiple human pathogens, including Mycobacterium tuberculosis. The toxin, MbcT, is bactericidal unless neutralized by its antitoxin MbcA. To investigate the mechanism, we solved the 1.8 A-resolution crystal structure of the MbcTA complex. We found that MbcT resembles secreted NAD+-dependent bacterial exotoxins, such as diphthe...
10 CitationsSource
#1Uday Tak (UAB: University of Alabama at Birmingham)H-Index: 2
#2Jiri Vlach (UAB: University of Alabama at Birmingham)H-Index: 6
Last. Michael Niederweis (UAB: University of Alabama at Birmingham)H-Index: 44
view all 8 authors...
: Upon host infection, Mycobacterium tuberculosis secretes the tuberculosis necrotizing toxin (TNT) into the cytosol of infected macrophages, leading to host cell death by necroptosis. TNT hydrolyzes NAD+ in the absence of any exogenous cofactor, thus classifying it as a β-NAD+ glycohydrolase. However, TNT lacks sequence similarity with other NAD+ hydrolyzing enzymes and lacks the essential motifs involved in NAD+ binding and hydrolysis by these enzymes. In this study, we used NMR to examine the...
5 CitationsSource
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