Mechanisms of Resistance to Antibiotics
Code
21221
Academic unit
NOVA Medical School | Faculdade de Ciências Médicas
Department
Medical Bacteriology/Genetics
Credits
6
Teacher in charge
Profª Doutora Isabel Maria dos Santos Leitão Couto
Teaching language
Portuguese
Objectives
1. To know the main examples of antibiotic resistant bacteria in the hospital and in the community. To be able to interpret and describe the associated resistance mechanisms.
2. To understand the intracellular action of antibiotics.
3. To understand the importance of bacterial biofilm formation on the development of resistance to antimicrobials.
4. To have a global perspective on the impact of antibiotics on the environment and understand the One Health concept.
5. To be able to interpret data on antibiotic susceptibility laboratorial tests.
6. To be able to design and perform independently experimental protocols to determine the mechanism(s) of resistance to a given antibiotic.
Prerequisites
n/a
Subject matter
Theoretical:
1-The resistance to antibiotics in the 21st century.
2-Main bacterial mechanisms of resistance to antibiotics.
3-Antibiotic resistant bacteria in the hospital and the community: key examples. Strains MRSA, VISA/VRSA; VRE; multidrug/extensively drug resistant M. tuberculosis (M/XDRTB), Gramnegative bacteria producers of ESBLs and carbapenemases.
4-Intracellular action of antibiotics.
5-Bacterial biofilms and resistance.
6-Other antimicrobials: mechanisms of action and resistance.
7-Antibiotics in the environment. The One Health concept.
Practical:
Laboratorial resolution of casestudies; determination of mechanisms of resistance to antibiotics in isolates of E. coli and Staphylococcus aureus. Performance of susceptibility assays for antibiotics of several classes by disk diffusion and determination of minimum inhibitory concentration (MIC); screening of resistance determinants; evaluation of the effect of different resistance mechanisms on the phenotypes detected.
Bibliography
- Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015 Jan;13(1):4251.
- de Sousa JCF & Peixe LV (2010) Antibióticos Antibacterianos. In Microbiologia, pp453469, WF Canas Ferreira, JCF de Sousa, N Lima (ed). Lidel.
- Livermore DM (2012). Fourteen years in resistance (review). Int. J. Antimicrob. Agents. 9:283 294.
- Magiorakos A.P. et al. (2012) Multidrugresistant, extensively drugresistant and pandrugresistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect; 18: 268281.
- Nature Vol. 509, No. 7498 Suppl. Antibiotics, pp S1S43 (2014)
-Theuretzbacher, U (2012) Accelerating resistance, inadequate antibacterial drug pipelines and international responses (review). Int. J. Antimicrob. Agents. 39: 295 299.
Teaching method
The Curricular Unit "Mechanisms of Antibiotic Resistance" starts from several concepts of bacteriology and antibiotic therapy, already discussed in Curricular Units of the first semester of the Master Course in Medical Microbiology and lead the student to explore them from new perspectives, aiming to understand that resistance to antibiotics often results from a multifactorial set of circumstances where antibiotic, microorganism, host and environment, all play a role that can lead to the emergence of resistance and subsequent treatment failure.
Lectures describe the most significant antibioticresistant bacteria, in hospital or in the community. These examples illustrate the different mechanisms of resistance to antibiotics and are starting points for understanding the different factors that can lead to emergence and dissemination of resistant strains. Additional aspects addressed include biofilm formation, the massive use of other antimicrobial compounds, such as biocides and the presence of antibiotics and biocides in the environment as factors that may contribute to increased resistance to antibiotics. The intracellular action of antibiotics is also addressed, drawing calling the student's attention to the importance of the host in the success of therapy.
This Curricular Unit also includes a laboratory component, in which, after a first step of susceptibility assays for a specific set of antibiotics and bacteria, students are asked to formulate hypotheses about possible mechanism(s) that may explain some of the observed resistance phenotypes and to draw an experimental strategy to (i) test the hypotheses formulated and (ii) conclude about the resistance mechanisms concerned.
This will require students to apply the information provided in the lectures as well as in literature (scientific papers), available for consultation.
This approach aims to provide to student the opportunity to develop skills on the design and independent analysis of experiments, which will be required for their dissertation work when, as in this Curricular Unit, they are confronted with results that require interpretation, using the knowledge and literature available in a continuous formulation of hypotheses, interpretation and new approaches.
The theoretical concepts are taught by an expositive method, promoting interaction with students. The laboratory classes are carried out in groups (2-4 students/group) in which each group will receive several bacterial strains for which it shall determine the phenotype (susceptible/resistant) towards several antibiotics; design and execute several experiments to determine the possible mechanisms behind specific resistance phenotypes.
Evaluation method
· Written exam of multiple choice questions, focusing on the content of theoretical classes (60% total classification)
· Preparation, presentation and discussion of the practical case-study (40% total classification).
Both components are rated in a 0 to 20 values scale; students rated 9.5 or higher in both components (theoretical exam and case-study presentation) will be approved.