Group Leader/s

 

intro

Pathogenic bacteria are increasingly resistant to antibiotics. Among the few alternatives that are glimpsed to treat this problem are endolysins encoded by phages, modular enzymes that hydrolyze specific bonds of bacterial peptidoglycan. New phage endolysins are being tested or by construction of chimeras fusing different functional domains. These enzymes are effective in both planktonic cultures and in biofilms. Specifically, during 2017, the molecular basis of the recognition of the cell wall by endolysin Cpl-7 (encoded by a pneumococcal phage) was studied. In addition, a new chimeric enzyme (Csl2) has been constructed which has shown its bactericidal activity in infections caused by Streptococcus suis, an emerging zoonotic agent. Validation of in vitro results is done in mouse or zebrafish models.

Most chronic infections are caused by bacteria that grow into biofilms. The antibiotic tolerance of these communities is well known. Frequently, the human nasopharynx is colonized by encapsulated pneumococci associated with non-encapsulated pneumococci and non-typeable H. influenzae (NTHi) strains. During 2017 the requirements for the formation of mixed in vitro biofilms between S. pneumoniae and NTHi strains were studied. This model has been used to demonstrate the antibiofilm activity of two antioxidants frequently used in clinical practice: N-acetyl-L-cysteine and cysteamine. Moreover, a novel procedure allowing the specific recognition of S. pneumoniae in mixed cultures has been developed. This method involves the use of the HPA lectin from Helix pomatia.

Key words: Streptococcus pneumoniae, virulence, immunity, complement system, carrier state, choline-binding proteins, biofilms, enzybiotics, bacteriophages, structure-function.

 

Vazquez R, Domenech M, Iglesias-Bexiga M, Menendez M, Garcia P  [2017]. Csl2, a novel chimeric bacteriophage lysin to fight infections caused by Streptococcus suis, an emerging zoonotic pathogen. Sci Rep 7:16506. https://doi.org/10.1038/s41598-017-16736-0.

Domenech M, García E  [2017]. N-Acetyl-L-cysteine and cysteamine: new strategies against mixed biofilms of non-encapsulated Streptococcus pneumoniae and non-typeable Haemophilus influenzae. Antimicrob Agents Chemother 61:e01992-16. https://doi.org/10.1128/AAC.01992-16

Bustamante N, Iglesias-Bexiga M, Bernardo-García N, Silva-Martín N, García G, Campanero-Rhodes MA, García E, Usón I, Buey RM, García P, Hermoso JA, Bruix M, Menéndez M  [2017]. Deciphering how Cpl-7 cell wall-binding repeats recognize the bacterial peptidoglycan. Sci Rep 7:16494. https://doi.org/10.1038/s41598-017-16392-4

Domenech M, Pedrero-Vega E, Prieto A, García E.  [2016]. Evidence of the presence of nucleic acids and β-glucan in the matrix of non-typeable Haemophilus influenzae in vitro biofilms. Sci Rep 6:36424. Doi:10.1038/srep36424

Corsini B, Aguinagalde L, Ruiz S; Domenech M, Antequera M, Fenoll A, García P, García E, Yuste J  [2016]. Immunization with LytB protein of Streptococcus pneumoniae activates complement-mediated phagocytosis and induces protection against pneumonia and sepsis. Vaccine 34:6148–6157. htpps://doi.org/10.1016/j.vaccine.2016.11.001

 

Funding

— MCyT, BMC2000-1002 (2000-2003).

— Fundación Ramón Areces (2000-2003).

— BIO2000-0009-P4-04 (2001-2005).

— MCyT, BMC2003-00074 (2003-2006).

— Ministerio de Sanidad y Consumo, Redes G03/103 y C03/104.

— MCyT, SAF2006-00390 (2006-2009)

— Member of the CIBER of Respiratory Diseases (Instituto de Salud Carlos III)

– CAM, COMBACT Program, S-BIO-0260/2006 (2007-2010)

– MICINN, SAF2009-10824 (2010-2012)

– MICINN, IPT-2011-1337-010000

- MINECO, SAF2012-39444-C02-01 (2013-2015)