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Molecular Genetics of Microbial Resistance

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The Molecular Genetics of Microbial Resistance Laboratory mainly focus on understanding the survival mechanisms of human pathogens that relate to oxidative and nitrosative stress imposed by the human immune system.

 

 


Lígia M. Saraiva
Investigadora Principal (Habilitation)
PhD in Biochemistry, Universidade Nova de Lisboa

Phone (+351) 214469328 | Extension 1328
lst@itqb.unl.pt

 

Research Interests

Infections caused by bacterial pathogens represent an increasing threat to global public health as many strains are rapidly becoming resistant to all available antibiotics. Therefore, understanding how pathogens resist immunity and identifying novel targets for therapeutic intervention is crucial to successfully treat  infectious diseases.

One of the research topics of the laboratory concerns the study of the mechanisms used by pathogens such as Staphylococcus aureus , Helicobacter pylori  and Escherichia coli to resist nitrosative and oxidative stresses, which are key weapons of the mammalian immune system’s to kill invading microorganisms.

The laboratory is also involved in the study of novel antimicrobial drugs, the carbon monoxide releasing compounds (CO-RMs), which represent a novel class of compounds that cause the rapid death of pathogenic bacteria. Envisaging the future utilization in the battle against antibiotic resistance, we have been exploring the mechanisms that underpin CO-RMs antibacterial action.

The third research topic of the group concerns the study of the sulfate-reducing bacteria of the Desulfovibrio genus. These anaerobic microorganisms are environmentally important due to their ability to immobilize soluble forms of toxic metals like uranium, arsenate and chromate. Importantly, sulfate-reducing bacteria are also part of the normal human gut flora. However, more recently, some species of Desulfovibrio have been linked to infectious processes as these microorganisms were isolated from abscesses. In Desulfovibrio, we are investigating the biosynthesis of heme, which is the component that gives blood its colour and allows the red blood cells to carry oxygen in our body, as well as the mechanisms of oxygen tolerance and the iron metabolism.

To address these areas of research, the group combines a wide range of methodologies, like genomics, transcriptomics, microbiology, molecular genetics, biochemistry, and mammalian cell culture technology 

 

Group Members

Laboratory's Website

For further information please visit the laboratory's website


Selected Publications

  1.  Tavares AF, Pa rente MR, Justino MC, Oleastro M, Nobre LS, Saraiva LM. (2013) The bactericidal activity of carbon monoxide-releasing molecules against Helicobacter pylori. PLoS One. Dec 26;8(12):e83157.
  2.  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.
  3. Bali S, Lawrence AD, Lobo SA, Saraiva LM, Golding BT, Palmer DJ, Howard MJ, Ferguson SJ, Warren MJ. (2011) Molecular hijacking of siroheme for the synthesis of heme and d1 heme. Proc Natl Acad Sci USA, 108, 18206-5.
     

 > Complete list

 

Genética Molecular da Resistência Microbiana (PT)

No nosso grupo estudamos os mecanismos que os microorganismos patogénicos utilizam para sobreviver aos compostos químicos gerados pelo sistema imunitário. Em particular, os humanos produzem óxido nítrico e espécies reactivas do oxigénio para combater infecções virais, bacterianas ou causadas por parasitas. Pretendemos identificar e estudar a função e regulação de genes responsáveis pela sobrevivência dos microorganismos a estes stresses, utilizando uma abordagem genética, microbiana e bioquímica. Assim conseguir-se-á elucidar como resistem os microorganismos à barreira de protecção criada pelo nosso sistema imunitário, informação que é crucial para o desenvolvimento de estratégias que diminuam a sua resistência. De facto, a resistência dos patogénios aos antibióticos clássicos é actualmente um dos maiores problemas que a medicina enfrenta, sendo causadora de um elevado número de mortes, especialmente em ambientes hospitalares. A descoberta de novos fármacos que tenham princípios activos distintos dos antibióticos actuais é um dos grandes desafios da investigação fundamental e biomédica. Neste sentido, o nosso grupo descobriu recentemente que o monóxido de carbono tem a capacidade de matar bactérias tendo potencialidades para vir a constituir um novo tipo de antibiótico, encontrando-se agora em estudo o seu modo de acção.

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