Abstract
The activation of the β-class carbonic anhydrases (CAs, EC 4.2.1.1) from the bacteria Brucella suis and Francisella tularensis with amine and amino acids was investigated. BsuCA 1 was sensitive to activation with amino acids and amines, whereas FtuCA was not. The most effective BsuCA 1 activators were L-adrenaline and D-Tyr (KAs of 0.70–0.95 µM). L-His, L-/D-Phe, L-/D-DOPA, L-Trp, L-Tyr, 4-amino-L-Phe, dopamine, 2-pyridyl-methylamine, D-Glu and L-Gln showed activation constants in the range of 0.70–3.21 µM. FtuCA was sensitive to activation with L-Glu (KA of 9.13 µM). Most of the investigated compounds showed a weak activating effect against FtuCA (KAs of 30.5–78.3 µM). Many of the investigated amino acid and amines are present in high concentrations in many tissues in vertebrates, and their role in the pathogenicity of the two bacteria is poorly understood. Our study may bring insights in processes connected with invasion and pathogenic effects of intracellular bacteria.
Highlights
The pathogenic bacteria Brucella suis[1,2] and Francisella tularensis[3,4] provoke serious diseases both in human and livestock, are difficult to treat by antibiotics, and have the potential to induce widespread infections
Natural and non-natural amino acids and amines 1–24 were included among the investigated compounds as activators of the two bacterial b-CAs investigated here (Figure 1)
The Michaelis constant of hCA I and II is in the range of 4.0–9.3 mM, whereas for the bacterial enzymes the KM values are in the range of 11.0–16.4 mM, denoting that CO2 has a lower affinity for the bacterial enzymes than for the human ones hCA I/II
Summary
The pathogenic bacteria Brucella suis[1,2] and Francisella tularensis[3,4] provoke serious diseases both in human and livestock, are difficult to treat by antibiotics, and have the potential to induce widespread infections. Both Brucella and Francisella might be used as bioterrorism organisms due to the fact that quite low doses of pathogens (as few as 10–100 bacteria) are highly infectious, leading to ravaging epidemics[1]. Searching for new drug targets addressing these complex issues is of stringent relevance
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