Gene Expression Regulation in Bacterial Pathogens and Antimicrobial Strategies

• Mechanisms of gene expression regulation in bacteria

The survival of bacteria to adverse conditions depends on its ability to modulate gene expression, to provide the appropriate gene products for the adaptation to the new environmental conditions. In the case of pathogenic bacteria, the modulation of gene expression is crucial, since during the infectious process they need to encounter different many different niches of the host. In our research group, we are studying different mechanisms of gene expression regulation in Salmonella enterica and Escherichia coli. The studies in Salmonella are focused in the regulation of the pathogenicity island 1 genes, which are involved in the invasion of epithelial cells. In Escherichia coli, mechanisms involved in the control of the expression of the alpha hemolysin produced by uropathogenic isolates and the flagella production are being explored.

• Biofilms in Salmonella

Bacteria are often growing as communities attached to surfaces, forming the so-called biofilms. Within the biofilms, the bacterial cells are embedded in a polysaccharide matrix. Growth in form of biofilms provide to the bacteria resistance to survive adverse conditions. In general, when bacteria grow forming biofilm became more resistant to antibiotics and disinfectants. In food industry, the bacterial biofilms have a negative impact from both economical and sanitary point of view. Since biofilms are more resistant to disinfectants, often are sources of food contamination. In our research group, we are studying which mechanisms are involved in the control of biofilm formation in Salmonella and Escherichia coli. Moreover, we are searching for compounds with activity to either avoid biofilm production or promote disaggregation of existing biofilms of Salmonella.

• Bacterial conjugation

Conjugative plasmids are vehicles for horizontal gene transfer. Conjugation is one of the major mechanisms involved in the spread of antibiotic resistance determinants among bacteria. In our research group, during the last years we have been studying the biology of IncHI1 plasmids, which are involved in the multiresistance phenotype of Salmonella and other pathogenic bacteria. We have described a regulatory circuit, composed of three proteins, that controls the expression of genes involved in the conjugation of IncHI1 plasmids in response to changes in the environmental conditions.

• Comparative studies of Campylobacter populations

Campylobacter is the causal agent of the highest incidence food-borne infection in the European Union. Campylobacter is a microaerophilic gram negative bacteria. Infection in humans is mostly due to consumption of chicken meat. It is consider a member of the commensal microbiota of chicken and other birds: The research project aims to analyze the existing diversity among Campylobacter isolates from wild birds, poultry and humans by monitoring differences in the profile of secreted proteins, plasmid content and antibiotic resistances. The main aim is to identify secreted factors involved in infection in humans as well as a relationship among those secreted proteins, antibiotic resistance and plasmid content.

• Fernández-Coll, L.; Potrykus, K., Cashel, M., Balsalobre, C. 2020. Mutational analysis of Escherichia coli GreA protein reveals new functional activity independent of antipause and lethal when overexpressed. Scientific reports. 10: 16074
• El Mouali, Y., Esteva-Martínez, G., García-Pedemonte, D., Balsalobre, C. 2020. Differential regulation of CsrC and CsrB by CRP-cAMP in Salmonella enterica. Frontiers in Microbiology. 11: 570536
• Cabrer-Panes, J.D., Fernández-Coll, L., Fernández-Vázquez, J., Gaviria-Cantin, T.C., El Mouali, Y., Aberg, A., Balsalobre, C. 2020. ppGpp mediates the growth phase-dependent regulation of agn43, a phase variable gene, by stimulating its promoter activity. Environmental Microbiology Reports. 12, 444-453
• Guirado, P., Paytubi, S., Miró, E., Iglesias-Torrens, Y., Navarro, F., Cerdà-Cuellar, M., Stephan-Otto Antolini, C., Balsalobre, C., Madrid, C., 2020. Differential distribution of the wlan and cgtB genes, associated with Guillain-Barré syndrome, in Campylobacter jejuni isolates from humans, broiler chickens, and wild birds. Microorganisms. 8, 325
• Cuevas-Ferrando, E., Guirado, P., Miró, E., Iglesias-Torrens, Y., Navarro, F., Alioto, T.S., Gómez-Garrido, J., Madrid, C., Balsalobre, C. 2020. Tetracycline resistance transmission in Campylobacter is promoted at temperatures resembling the avian reservoir. Veterinary Microbiology. 108652
• Gibert, M. Paytubi, S., Madrid, C, Balsalobre, C. 2020. Temperature dependent control of the R27 conjugative plasmid genes. Frontiers in Molecular Biosciences. 7, 124
• Dylewski, M. Fernéndez- Coll, L., Bruhn-Olszewska, Balsalobre, C., Potrykus, K. 2019. Autoregulation of greA expression relies on GraL rather than on greA promoter region. International Journal of Molecular Sciences. 20, 5224
• Luque, A., Paytubi, S., Sánchez-Miontejo, J., Gibert, M., Balsalobre, C., Madrid, C. 2019. Crosstalk between bacterial conjugation and motility is mediated by plasmid-borne regulators. Environmental Microbiology. 11: 708-717.
• El Mouali, Y., Balsalobre, C. 2019. 3’ untranslated regions: regulation at the end of the road. Current Genetics. 65:127–131
• El Mouali, Y., Gaviria-Cantin, T., Sánchez-Romero, M. A., Gibert, M., Westermann, A. J., Vogel, J., Balsalobre, C. 2018. CRP-cAMP mediates silencing of Salmonella virulence at the post-trancriptional level. PLoS Genetics. 14(6):e1007401
• Velasco, E., Wang, S., Sanet, M., Fernández-Vázquez, J., Jové, D., Glaría, E., Valledor, A. F., O’Halloran, T. V., Balsalobre, C. 2018. A new role for Zinc limitation in bacterial pathogenicity: modulation of α-hemolysin from uropathogenic Escherichia coli. Scientific reports. 8:6535
• Iglesias-Torrens, Y., Miró, E., Guirado, P., Llovet, T., Muñoz, C., Cerdà-Cuellar, M., Madrid, C., Balsalobre, C., Navarro, F. 2018. Population structure, antimicrobial resistance, and virulence-associated genes in Campylobacter jejuni isolated from three ecological niches: gastroenteritis patients, broilers, and wild birds. Frontiers in Microbiology. 9:1676
• Gaviria-Cantin, T., El Mouali, Y., Le Guyon, S., Römling, U., Balsalobre, C. 2017. Gre factors-mediated control of hilD transcription is essential for the invasion of epithelial cells by Salmonella enterica serovar Typhimurium. PLoS Pathogens. 13 - 4,
• Paytubi, S., Cansado, C., Madrid, C., Balsalobre, C. 2017. Nutrient composition promotes switching between pellicle and bottom biofilm in Salmonella. Frontiers in Microbiology 8:2160
• Paytubi, S., de la Cruz, M., Tormo, J.R., Martín, J., González, I., González-Menendez, V., Genilloud, O., Reyes, F., Vicente, F., Madrid, C., Balsalobre, C. 2017.A high throughput screening platform of microbial natural products for the discovery of molecules with antibiofilm properties against Salmonella. Frontiers in Microbiology 8: 326
• Gibert, M., Paytubi, S., Beltrán, S., Juárez, A., Balsalobre, C., Madrid, C. 2016. Growth phase-dependent control of R27 conjugation is mediated by the interplay between the plasmid encoded regulatory circuit TrhR/TrhY-HtdA and the cAMP regulon. Environmental Microbiology 18:5277-5287

Interplay between conjugative plasmids and the bacterial chromosome: characterization of the impact in the physiology and the regulatory mechanisms involved. Ministerio de Economia y Competitividad. PGC2018-096958-B-I00. 2019-2022

Molecular Biology of bacterial pathogens and antimicrobial strategies. Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR). 2017SGR499. 2017-2020

Identification of factors involved in food borne campylobacteriosis. Ministerio de Economia y Competitividad. AGL2013-45339-R. 2014-2017

“Searching for new anti-biofilm strategies to control Salmonella contamination in the food industry” RecerCaixa. 2012/ACUP/00048. 2013-2015