The Carbapenemase BKC-1 from Klebsiella pneumoniae Is Adapted for Translocation by Both the Tat and Sec Translocons

Abstract

Bacteria can readily acquire plasmids via lateral gene transfer (LGT). These plasmids can carry genes for virulence and antimicrobial resistance (AMR).

PncsHub: a platform for annotating and analyzing non-classically secreted proteins in Gram-positive bacteria

“…The spread of virulence factors by horizontal gene transfer separates the most pathogenic bacteria from the rest. And it is the presence of robust and flexible secretion machinery that becomes essential for recipient cells to utilize these ‘alien’ protein sequences ( 81 , 82 ). Recently, there have been several interesting reports of bacteria secreting recombinant proteins (derived from another bacterium) through their own non-classical secretion systems.…”

The biogenesis of β-lactamase enzymes

“…β-Lactamase signal sequences for enzymes known to be translocated through the Sec and Tat pathways are shown (single-letter amino acid code is used for simplicity), along with a schematic representation of the type of signal peptide for each case; the scissors indicate the position of the signal peptidase cleavage site. *BKC-1 from Klebsiella has been known to engage both Sec and Tat translocons in that organism [178], whereas the export route of Shinella BKC-1 has not been elucidated in the native organism.…”

“…Notably, the genetic locus of β-lactamase enzymes seems to correlate with their translocation process. In particular, plasmid-associated β-lactamases, such as AmpC, CTX-M-14, TEM-1 [177], and KPC-2 [178] are always translocated via the Sec system, but enzymes encoded on bacterial chromosomes, for example L2 (177), BlaC [179], and PenA [180], can also be exported through the Tat pathway. Therefore, it is worth keeping in mind that the origin of the β-lactamase could play a crucial role in signal sequence adaptability, along with other factors that affect the folding and translocation kinetics of these enzymes.…”

“…maltophilia [177], and most recently for the carbapenemase KPC-2 from K. pneumoniae [178]. Notably, all metallo-β-lactamase enzymes studied to date, undergo Sec transport, a step critical for selective acquisition of Zn(II) ions in the periplasm [82], and it is thus likely that all enzymes of this family are Sec substrates.…”

“…coli and K. pneumoniae [178]. This dual-targeted translocation was attributed to the presence of a twin arginine motif in addition to a duplicated sequence of 16, predominantly hydrophobic, amino acids at its N-terminus (); these may have evolved in K.…”