Molecular Mechanisms of Pathogen Resistance

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Research

Selected Publications

Staphylococcus aureus Fighting the innate immune system

Carvalho SM, Freitas CS, Oliveira AS, and Saraiva LM (2021) Staphylococcus aureus flavohaemoglobin contributes to early stage biofilm development under nitrosative stress FEMS Microbiol. Lett., in press

Videira MAM, Lobo SAL, Sousa FL, Saraiva LM. (2020) FEBS J. Identification of the sirohaem biosynthesis pathway in Staphylococcus aureus. 287,1537-1553

Videira MAM, Lobo SAL, Silva LSO, Palmer DJ, Warren MJ, Prieto M, Coutinho A, Sousa FL, Fernandes F, Saraiva LM. (2018) Staphylococcus aureus haem biosynthesis and acquisition pathways are linked through haem monooxygenase IsdG. Mol Microbiol. 109(3):385-400.

Carvalho SM, de Jong A, Kloosterman TG, Kuipers OP, Saraiva LM. (2017) The Staphylococcus aureus α-Acetolactate Synthase ALS Confers Resistance to Nitrosative Stress. Front Microbiol. Jul 11;8:1273.

Lobo SAL, Scott A, Videira MAM, Winpenny D, Gardner M, Palmer MJ, Schroeder S, Lawrence A, Parkinson T, Warren MJ, and Saraiva LM (2015) Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway. Mol. Microbiol., 97(3):472-87.

Nobre LS and Saraiva LM. (2013) Effect of combined oxidative and nitrosative stresses on Staphylococcus aureus transcriptome. Appl. Microbiol. Biotechnol. 97, 2563-73.

Nobre LS, Todorovic S, Tavares AFN, Oldfield P, Hildebrandt P, Teixeira M, and Saraiva, LM (2010) Binding of azole antibiotics to Staphylococcus aureus flavohemoglobin increases intracellular oxidative stress, J. Bacteriol. 192, 1527-33.

Tavares AFN, Nobre LS, Melo AMP, and Saraiva LM. (2009) A novel nitroreductase of Staphylococcus aureus with S-nitrosoglutathione reductase activity. J. Bacteriol. 191, 3403-3406.

Helicobacter species Living in a nitrite rich environment

Parente MR, Forte E, Falabella M, Boneca IG, Teixeira M, Giuffrè A, Saraiva LM. (2017) Nitrosative stress defences of the enterohepatic pathogenic bacterium Helicobacter pullorum. Sci Rep. Aug 30;7(1):9909.

Flint A, Stintzi A Saraiva LM (2016) Oxidative and nitrosative stress defences of Helicobacter and Campylobacter species that counteract mammalian immunity. FEMS Microbiol Rev. Nov 1;40(6):938-960..

Parente MR, Monteiro JT, Martins GG, and Saraiva LM (2016) Helicobacter pullorum induces in murine macrophages nitric oxide release that promotes phagocytosis and killing, Microbiology. 162:503-12

Justino MC, Parente MR, Boneca IG, and Saraiva LM (2014) FrxA is a GSNO reductase enzyme that contributes to Helicobacter pylori pathogenicity. FEBS J. 281, 4495-4505.

Justino MC, Ecobichon C, Fernandes AF, Boneca IG, Saraiva LM. (2012) Helicobacter pylori has an unprecedented nitric oxide detoxifying system. Antioxid. Redox. Signal. 17, 1190-200.

Staphylococcus aureus

Desulfovibrio spp.

Heme biosynthesis

Zamarreno JB, Videira MAM , and Saraiva LM (2021) Regulation of bacterial haem biosynthesis. Coord. Chem. Reviews, in press.

Videira MAM, Lobo SAL, Sousa FL, Saraiva LM. (2020) FEBS J. Identification of the sirohaem biosynthesis pathway in Staphylococcus aureus. 287,1537-1553

Lobo SA, Videira MA, Pacheco I, Wass MN, Warren MJ, Teixeira M, Matias PM, Romão CV, and Saraiva LM. 2017. Desulfovibrio vulgaris CbiKP cobaltochelatase: evolution of a haem binding protein orchestrated by the incorporation of two histidine residues. Environ Microbiol. 19, 106-118.

Lobo SAL, Lawrence AD, Romão CV, Warren MJ, Teixeira M, and Saraiva LM (2014) Characterization of Desulfovibrio vulgaris haem b synthase, a radical SAM family member. BBA Proteins and Proteomics, 1844, 1238-47.

Bali S, Lawrence AD, Lobo SA, Saraiva LM, Golding BT, Palmer DJ, Howard MJ, Ferguson SJ and Warren MJ. (2011) Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc. Natl. Acad. Sci USA, 108, 18206-5.

Romão CV, Ladakis D, Lobo SA, Carrondo MA, Brindley AA, Deery E, Matias PM, Pickersgill MW, Saraiva LM and Warren MJ (2011) Evolution in a family of chelatases facilitated by the introduction of active site asymmetry and protein oligomerization. Proc. Natl. Acad. Sci. USA.108, 97-102.

*Escherichia coli*		Nitrosative/oxidative stress defences against mammalian macrophages
		Silva LSO, Matias PM, Romão CV, Saraiva LM. (2021) Structural Basis of RICs Iron Donation for Iron-Sulfur Cluster Biogenesis. Front Microbiol. 12:670681. Silva LSO, Baptista JM, Batley C, Andrews SC, Saraiva LM. ( 2018) The Di-iron RIC Protein (YtfE) of Escherichia coli Interacts with the DNA-Binding Protein from Starved Cells (Dps) To Diminish RIC Protein-Mediated Redox Stress. J Bacteriol. pii: e00527-18 Silva LO, Nobre LS, Mil-Homens D, Fialho A, Saraiva LM. (2018) Repair of Iron Centers RIC protein contributes to the virulence of Staphylococcus aureus. Virulence. 9:1, 312-317 Nobre LS, Meloni D, Teixeira M, Viscogliosi E, and Saraiva LM (2016) Trichomonas vaginalis Repair of Iron Centres proteins: the different role of two paralogs. Protist. 167, 222–233. Nobre LS, Lousa D, Pacheco I, Soares CM, Teixeira M and Saraiva LM (2015) Insights into the structure of the diiron site of RIC from Escherichia coli. FEBS Lett. 589 (4):426-431. Nobre LS, Garcia-Serres R, Todorovic S, Hildebrandt P, Teixeira M, Latour JM, and Saraiva LM. (2014) Escherichia coli RIC is able to donate iron to iron-sulfur clusters. PLOS One , 16, 9(4), e95222. Justino MC, Almeida CC, Teixeira M, and Saraiva LM. (2007) Escherichia coli di-iron YtfE protein is necessary for the repair of stress damaged iron-sulfur clusters. J. Biol. Chem. 282, 10352-10359.
CORMs		New antibiotics
		Mendes SS, Miranda V, Saraiva LM. (2021) Antioxidants (Basel). Hydrogen Sulfide and Carbon Monoxide Tolerance in Bacteria. 10, 729. Carvalho SM, Marques J, Romão CC, Saraiva LM (2019) Metabolomics of Escherichia coli Treated with the Antimicrobial Carbon Monoxide-Releasing Molecule CORM-3 Reveals Tricarboxylic Acid Cycle as Major Target. Antimicrob Agents Chemother. pii: e00643-19 Nobre LS, Jeremias H, Romão CC and Saraiva LM (2016) Examining the antimicrobial activity and toxicity to animal cells of different types of CO-releasing molecules, Dalton Trans. 45,1455-66. Tavares AF, Parente MR, Justino MC, Oleastro M, Nobre LS, and Saraiva LM. (2013) The bactericidal activity of carbon monoxide-releasing molecules against Helicobacter pylori. PLoS One. 8(12):e83157. Tavares AF, Teixeira M, Romao CC, Seixas JD, Nobre LS, and Saraiva LM. (2011) Reactive oxygen species mediate bactericidal killing elicited by carbon monoxide-releasing molecules. J. Biol Chem. 286, 26708-17. Nobre LS, Seixas JD, Romão CC, and Saraiva LM. (2007) The antimicrobial action of carbon monoxide releasing compounds. Antimicrob. Agents Chemother. 51, 4303-07.

Keywords

Staphylococcus aureus, Helicobacter pylori, Desulfovibrio, sulphate-reducing bacteria, Escherichia coli;

Bacteria, anaerobic microorganisms, pathogen, antibiotic, antibiotic resistance, immune system, carbon monoxide, iron metabolism, heme;

Cell culture, molecular genetics, genomics, transcriptomics, microbiology, biochemistry.

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Pubmed Link

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Group Members

		Lígia M. Saraiva Head of Laboratory Habilitacion (Agregação), ITQB-Universidade Nova de Lisboa Ph.D in Biochemistry - Biochemical Physics, Universidade Nova de Lisboa Degree in Chemical Engineering, Instituto Superior Técnico Phone: 214469328. E-mail: lst@itqb.unl.pt
		Sandra Carvalho Post-Doctoral Researcher Ph.D in Biochemistry, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa Degree in Biochemistry, Faculdade de Ciências e Tecnologia da Universidade de Coimbra Phone: 214469329. E-mail: smcc@itqb.unl.pt Discover novel mechanisms of resistance to nitrosative stress
		Marco Videira Post-Doctoral Researcher Ph.D in Biochemistry, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa Master in Biomedical Sciences, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa Degree in Biochemistry, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa Phone: 214469329. E-mail: m.videira@itqb.unl.pt Tetrapyrrole biosynthesis in Staphylococcus aureus
		Zamarreno Beas Post-Doctoral Researcher Ph.D in Microbiology, Centre Nationale de Recherche Scientific, Université Aix-Marseille Degree In Microbiology Biotechnology and Vegetal Biology, Université Aix-Marseille Phone: 214469329. E-mail: jzamarreno@itqb.unl.pt Tetrapyrrole biosynthesis in Campylobacter jejuni
		Liliana Silva Ph.D student Master in Clinical Analysis, Faculdade de Farmácia da Universidade de Coimbra Degree in Bioanalytical Sciences, Faculdade de Farmácia da Universidade de Coimbra Phone: 214469329. E-mail: lsilva@itqb.unl.pt Study of RIC proteins of Escherichia coli and Staphylococcus aureus
		Ana Sofia Mendes Ph.D student Master in Biochemistry for Health, Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa Degree in Cellular and Molecular Biology, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa Phone: 214469329. E-mail: ass.mendes@itqb.unl.pt Study of the antimicrobial properties of carbon monoxide-releasing molecules (CORMs)
		Joana Sofia Monteiro Batista Ph.D student Master in Translational Cardiovascular Medicine, University of Bristol, United Kingdom Degree in Clinical Analysis and Public Health, Escola Superior de Tecnologias de Lisboa (ESTEsL), Portugal Phone: 214469329. E-mail: joana.batista@itqb.unl.pt Study of tetrapyrrole homeostasis in gut pathogens
		Ana Rita Oliveira Ph.D student Master in Biotechnology, Faculdade de Ciências e Tecnologia da Universidade Nova de Lisboa Degree in Biomedical Sciences, Universidade de Aveiro Phone: 214469329. E-mail: ars.oliveira@itqb.unl.pt Study of the resistance of S. epidermidis to nitrosative stress

Former members

Jacqueline Fernandes, Cristiano Conte, Alexandra Lourenço, Paula Lourenço, Helena Duarte, Rute Valente, Susana Pascoal, Patricia Noronha da Costa (PhD), Claudia Almeida, Vera Gonçalves (PhD), Joana Baptista (PhD), Ana Filipa Tavares (PhD), Marta Campos Justino (PhD), Mafalda Figueiredo (PhD), Sara Sousa, Sofia Costa, Vera Mónica Gonçalves, Nuno Carvalho, Mafalda Barros, Catarina Godinho, Luis Sobral, Fábio Pereira, Cláudia Ribeiro, Ana Antão, Inês Ladeira, Inês Santos, Roberta Benedetto, Lígia Nobre, Margarida Parente, Susana Lobo, Patrícia Ferreira, Cátia Família, Joana Marques, Cláudia Freitas.