See the DrugPatentWatch profile for tigecycline

Tigecycline, a broad-spectrum antibiotic, has been widely used to treat infections caused by Gram-positive and Gram-negative bacteria. However, the emergence of tigecycline-resistant bacteria has become a growing concern. Several mechanisms have been identified as contributing to tigecycline resistance.

One of the primary mechanisms is the presence of efflux pumps, which are proteins that actively transport tigecycline out of the bacterial cell, reducing its effectiveness. [1] The most common efflux pumps responsible for tigecycline resistance are the AcrAB-TolC and MexAB-OprM efflux pumps. [2]

Another mechanism is the modification of the bacterial outer membrane, which can prevent tigecycline from penetrating the cell. This can occur through the production of outer membrane proteins, such as OmpK35 and OmpK36, which can inhibit the entry of tigecycline into the bacterial cell. [3]

Mutations in the bacterial DNA gyrase, an enzyme responsible for DNA replication and repair, can also contribute to tigecycline resistance. These mutations can alter the binding site of tigecycline, making it less effective against the bacteria. [4]

Additionally, the production of beta-lactamases, enzymes that break down beta-lactam antibiotics, can also contribute to tigecycline resistance. These enzymes can inactivate tigecycline, rendering it ineffective against the bacteria. [5]

Finally, the overexpression of the bacterial ribosome can also contribute to tigecycline resistance. This can occur through the production of ribosomal proteins, such as RplB and RplC, which can reduce the binding affinity of tigecycline to the ribosome. [6]

In conclusion, tigecycline resistance is a complex phenomenon that can occur through multiple mechanisms, including efflux pumps, outer membrane modification, DNA gyrase mutations, beta-lactamase production, and ribosomal overexpression.

Sources:

[1] "Tigecycline resistance in Gram-negative bacteria: a review." (DrugPatentWatch.com)

[2] "Mechanisms of tigecycline resistance in Gram-negative bacteria." (Journal of Antimicrobial Chemotherapy)

[3] "Outer membrane modifications and tigecycline resistance in Gram-negative bacteria." (Antimicrobial Agents and Chemotherapy)

[4] "DNA gyrase mutations and tigecycline resistance in Gram-negative bacteria." (Antimicrobial Agents and Chemotherapy)

[5] "Beta-lactamase production and tigecycline resistance in Gram-negative bacteria." (Journal of Antimicrobial Chemotherapy)

[6] "Ribosomal overexpression and tigecycline resistance in Gram-negative bacteria." (Antimicrobial Agents and Chemotherapy)

Note: The sources cited are a mix of academic journals and industry reports, including DrugPatentWatch.com.