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 . 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 . 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
Domenech M, García E. . Fluorescence imaging of Streptococcus pneumoniae with the Helix pomatia agglutinin (HPA) as a potential, rapid diagnostic tool. Front Microbiol 8:1333. https://doi.org/10.3389/fmicb.2017.01333
Blázquez B, Fresco-Taboada A, Iglesias-Bexiga M, Menéndez M, García P. . PL3 amidase, a tailor-made lysin constructed by domain shuffling with potent killing activity against pneumococci and related species. Front Microbiol 7:1156.
Domenech M, Ruiz S, Moscoso M, García E. . In vitro biofilm development of Streptococcus pneumoniae and formation of choline-binding protein–DNA complexes. Environ Microbiol Rep 7:715–727
Ramos-Sevillano E, Urzainqui A, de Andrés B, González-Tajuelo R, Domenech M, González-Camacho F, Sánchez-Madrid F, Brown JS, García E, Yuste J. . PSGL-1 on leukocytes is a critical component of the host immune response against invasive pneumococcal disease. PLoS Pathog 12:e1005500.
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 . 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
Díez-Martínez R, de Paz HD, García-Fernández E, Bustamante N, Euler CW, Fischetti VA, Menéndez M, García P . A novel chimeric phage lysin with high in vitro and in vivo bactericidal activity against Streptococcus pneumoniae. J Antimicrob Chemother 70:1763-1773
Domenech M, Pedrero-Vega E, Prieto A, García E. . 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 . 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
— 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)
International DropSens Award to the best research work in Applied Electroanalytical Chemistry. Malmö (Sweden). June 2014.