Figure 23–33 antibiotic targets. Although there are many antibiotics in clinical use, they have a narrow range of targets, which are highlighted in yellow. A few representative antibiotics in each class are listed. Nearly all antibiotics used to treat human infections fall into one of these categories. The vast majority inhibit either bacterial protein synthesis or bacterial cell wall synthesis.
Figure 23–34 Three general mechanisms of antibiotic resistance. (A) A nonresistant wild-type bacterial cell bathed in a drug (red triangles) that binds to and inhibits an essential enzyme (light green) will be killed due to enzyme inhibition. (B) A bacterium that has altered the drug’s target enzyme so that the drug no longer binds to the enzyme will survive and proliferate. In many cases, a single point mutation in the gene encoding the target protein can generate resistance. (C) A bacterium that expresses an enzyme (dark green) that either degrades or covalently modifies the drug will survive and proliferate. Some resistant bacteria, for example, make β-lactamase enzymes, which cleave penicillin and similar molecules. (D) A bacterium that expresses or up-regulates an efflux pump that ejects the drug from the bacterial cytoplasm (using energy derived from either ATP hydrolysis or the electrochemical gradient across the bacterial plasma membrane) will survive and proliferate. Some efflux pumps, such as the TetR efflux pump, are specific for a single drug (in this case, tetracycline), whereas others, called multidrug resistance (MDR) efflux pumps, are capable of exporting a wide variety of structurally dissimilar drugs. Upregulation of an MDR pump can render a bacterium resistant to a very large number of different antibiotics in a single step.
Because the acquisition of drug resistance is almost inevitable, it is crucial that we continue to develop innovative treatments for infectious diseases. We must also take additional measures to delay the onset of drug resistance.
All pathogens share the ability to interact with host cells in diverse ways that promote the replication and spread of the pathogen. Pathogens often colonize the host by adhering to or invading the epithelial surfaces that line the respiratory, gastrointestinal, and urinary tracts, as well as the other body surfaces in direct contact with the environment. Intracellular pathogens, including all viruses and many bacteria and protozoa, invade host cells by one of several mechanisms. Viruses rely largely on receptor-mediated endocytosis, whereas bacteria exploit cell adhesion and phagocytic pathways; in both cases, the host cell provides the machinery and energy for the invasion. Protozoa, by contrast, employ unique invasion strategies that usually require significant metabolic expense on the part of the invader. Once inside, intracellular pathogens seek out a cell compartment that is favorable for their survival and replication, frequently altering host membrane traffic and exploiting the host-cell cytoskeleton for intracellular movement. Pathogens evolve rapidly, so that new infectious diseases frequently emerge, and old pathogens acquire new ways to evade
What are the genetic and molecular features that differ between pathogens and members of the normal human microbiota? How can our immune system distinguish between the two?
To what extent are common host-cell biological pathways and molecules hijacked by diverse microbes?
Can host-cell defense molecules be mobilized by drugs to fight infection?
our attempts at treatment, prevention, and eradication.
Which statements are true? explain why or why not.
23–1 Our adult bodies harbor about 10 times more microbial cells than human cells.
23–2 The microbiomes from healthy humans are all very similar.
23–3 Pathogens must enter host cells to cause disease.
23–4 Viruses replicate their genomes in the nucleus of the host cell.