3.2.3 Porin expression and cephalosporin resistance in K. pneumoniae
K. pneumoniae bacteria express two major porins called OmpK35 and OmpK36. Expression of either of them is sufficient for the transport of β-lactam antibiotics across the cell membrane.
You may remember from Section 1.3 that reducing the number of porins in the cell wall can confer antibiotic resistance by preventing the antibiotic from crossing the membrane to reach its target. Therefore, you might expect that loss of either OmpK35 or OmpK36 from K. pneumoniae would result in resistance to cephalosporins. However, multiple studies have suggested that the loss of porins from the cell wall of K. pneumoniae does not result in clinically relevant resistance (Hernández-Allés et al., 2000). Therefore, infections caused by K. pneumoniae lacking porins can still be treated using β-lactam antibiotics.
Porin loss can contribute to cephalosporin resistance in bacteria with additional mechanisms of resistance. For example, the loss of OmpK35 and OmpK36 from the cell wall of ESBL-producing K. pneumoniae results in resistance to cefoxitin, a cephalosporin which is a poor ESBL substrate.
How might this affect the treatment of ESBL-producing K. pneumoniae?
Cefoxitin could be used to treat ESBL-producing K. pneumoniae because it is a poor substrate for ESBLs. However, if these K. pneumoniae strains do not express OmpK35 or OmpK36, cefoxitin will not be able to cross the outer membrane to reach its target.
Although you have largely considered each resistance mechanism separately this week, this example illustrates how bacteria may rely on multiple resistance mechanisms to protect themselves.