No formal prerequisite is required with respect to other courses.
However basic knowledge of general microbiology, basic immunology and microbial genetics is strongly recommended. This knowledge is normally acquired in the bachelor’s degrees that give access to the master’s degree in Medical Biotechnology and Nanobiotechnology.

Lectures

Part 1. The human microbiota, microbial virulence, antibiotic resistance and vaccines
The human microbiota.

Microbial pathogenesis and antibiotic resistance.
Vaccines.

Part 2. Drugs from microorganisms
Bioactive compounds from microorganisms.
Actinomycetes producing bioactive compounds.

Labs
Microbiome analysis, genome mining and new drug discovery.

Course outline and aims

The course aims to provide knowledge and skills to work professionally with roles of responsibility in the areas of medical biotechnology and nanobiotechnology which make use of micro-organisms or viruses (natural or genetically modified, whole or parts thereof) or which develop diagnostic devices and therapeutic to combat infectious and non-infectious diseases.

Learning outcomes

Knowledge to be attained:
• molecular and cellular mechanisms underlying microbial and viral pathogenicity

• molecular and cellular mechanisms underlying antibiotic-resistance
• methodological foundations for design and development of vaccines
• methodological foundations for discovery and production of bioactive compounds from microorganisms

Abilities to be attained:

• Analysis of DNA metabarcoding data
• New drug discovery from microorganisms by bioassays and genome mining
• Mutate-and-screen methods for microbial strain improvement

Learning methods consist of formal Lectures and Labs making use of slides and hypertext links to specific Web sites. Outside these activities, the students are expected to read assigned papers from the scientific literature.

Oral examination. It is aimed at ascertaining, in proportion:
- The level of theoretical knowledge through the presentation of the program topics (50%)
- The level of practical abilities through description of methods and methodologies (25%)
- The ability to apply theoretical knowledge and practical skills to solve simple problems (25%)

Programs of Lectures and Labs

Lectures

Part 1. The human microbiota, microbial virulence, antibiotic resistance and vaccines

The human microbiota. The human organism as an ecosystem: the holobiont theory. Host-microbiota interaction: general principles and mechanisms. Interactions between microorganisms: cooperation and competition strategies. Biodiversity and plasticity of the microbial ecosystem. Evolution of the human microbiota, life stages and lifestyles. The human microbiota in health and disease: eubiosis and dysbiosis. The stable normal flora of skin, oral cavity, respiratory tract, intestinal tract, urogenital tract. Dysbiosis and human diseases. Characterization of the microbiota at a structural and functional level: traditional and innovative methodological approaches. DNA metabarcoding and metagenomics. Phenotype microarrays. Modulation of the human microbiota: fecal transplantation, antibiotics, probiotics and phage therapy.

Microbial pathogenesis and antibiotic resistance. Infectivity, pathogenicity and virulence. The Koch’s postulates and their molecular version. Traditional pathogens, emerging pathogens and re-emerging pathogens. The next pandemic: antibiotic resistance. Natural function of antibiotics and ecological foundations of antibiotic resistance. Cellular and molecular basis of microbial pathogenesis and drug resistance. “Alien” DNA and evolution of virulence and antibiotic resistance. Virulence factors and toxins. Adhesion, invasion, growth/survival in host microenvironments. Quorum sensing. Biofilm. Evasion of innate and adaptive immunity. Regulation of virulence and antibiotic resistance genes. Models for the study of microbial pathogenesis: in vitro, in vivo and ex vivo experimental models. Methods to study microbial pathogenesis: Signature-tagged mutagenesis (STM); In vivo expression technology (IVET); Next-generation Sequencing-based approaches.

Vaccines. Historical notes on vaccines. Immunological principles. Conventional vaccines: killed or inactivated vaccines, attenuated live vaccines, subunit vaccines. Recombinant vaccines: recombinant viral vaccine, recombinant bacterial vaccine, genetically-attenuated live vaccines, edible vaccines. Reverse vaccinology.

Part 2. Drugs from microorganisms

Bioactive compounds from microorganisms. Chemical diversity and structural classes. Biological activity (antibiotic, antifungal, antiprotozoal, immunosuppressive, anticancer, etc.). Biosynthetic pathways: synthesis of precursor substrates, polyketides and polyketide synthase (PKS), oligopeptides and NRPS, PKS_NRPS hybrid systems, oligopeptides of ribosomal origin, oligosaccharides and terpenes, the main decoration reactions; manipulation of biosynthetic pathways.
Actinomycetes producing bioactive compounds. The life cycle and life style of the actinomycetes. Regulation of secondary metabolite biosynthesis: pathway-specific and pleiotropic regulators, extracellular signals, influence of nutrients. Strain improvement with classical methods and genetic engineering. Genome and transcriptome analysis of actinomycetes. New drug discovery by genome mining.

Labs
Microbiome analysis, genome mining and new drug discovery. Analysis of DNA metabarcoding data. Genome mining. Screening of bioactive compounds from environmental samples.

• G. Dehò, E. Galli. Biologia dei microrganismi. Edizione 2018. Casa Editrice Ambrosiana. Distribuzione esclusiva Zanichelli.
• S. Donadio, G. Marino. Biotecnologie microbiche. Edizione 2008. Casa Editrice Ambrosiana.

• M. Madigan, J. Martinko, K. Bender, D. Buckley, D. Stahl. Brock Biology of Microorganisms (14th Edition). Global Edition. Pearson.
• Y. K. Lee. Microbial Biotechnology (Third Edition). World Scientific.