Table 1.

Summary of proteases of bacterial and host origin implicated in gastrointestinal diseases.

Protease	Source	Classification	Activity/mechanism	Disease	Ref
Proteases released by bacteria
Collagenase A	Clostridium perfringens	Metalloprotease	Intestinal barrier alteration/mucus	IBD	124
Dipeptidyl peptidase IV Dipeptidase Amino peptidase C Tricorn protease homolog	Bacteroides/ B. vulgatus	Serine protease Metalloprotease Cysteine protease	Contribute to UC disease activity, barrier dysfunction	IBD	32,33
ND	R. mucilaginosa	ND	Gluten degradation	CeD	47
ND	Lactobacillus	ND	ATI peptides/gluten degradation	CeD	101
LasB	P. aeruginosa	Zn metalloprotease	Gluten degradation, PAR-2 mediated signaling Intestinal barrier alteration Degrade IL-2 and IFN-γ	CeD and others	18,146,162
Prolyl endopeptidases	F. meningosepticum S. capsulate M. xanthus	Serine peptidases	Gluten degradation	CeD	49
BAV86562.1 Subtilisin family	R. aeria	Serine protease	Gluten degradation	CeD	48
GeIE	E. faecalis	Metalloprotease	Compromise epithelial barrier	Colitis mouse model	131
SP-1	C. ramosum	Serine protease	Epithelial barrier dysfunction	Colitis mouse model	129
HtrA	H. pylori C. jejuni S. Typhimurium	Serine protease	Epithelial barrier alteration Growth and infection	Gastrointestinal infection	63,80,81
PqqE	H. pylori	Zn metalloprotease		Gastrointestinal infection
Haemagglutinin or vibriolysin	V. cholerae	Metalloprotease	Barrier integrity alteration/actin and tight junction rearrangement	Gastrointestinal infection	83
SepA	S. flexneri E. coli	Serine protease	Barrier dysfunction/invasion	Gastrointestinal infection	72
Pic	E. coli Citrobacter S. flexneri	Serine protease	Disrupt mucosal barriers/modulate immune response/ mucinase activity	Gastrointestinal infection	68–71
SslE	E. coli	Zn metalloprotease	Mucin degradation	Gastrointestinal infection	76
StcE	E. coli	Metalloproteases	Mucus degradation	Gastrointestinal infection	74,75
ND	L. pneumophila	Zn Metalloproteases	Degrade IL-2	Gastrointestinal infections	148
PROKKA_00509	Paraprevotella	ND	Trypsin degradation	Others	9
M60-like proteases	B. caccae	Metalloproteases	Mucin degradation	Other	127
M60-like/PF13402 domain	B. thetaiotaomicron	Metalloprotease	Mucin degradation	Others	125
ZmpB	C. perfringens	Zn metalloproteases	Mucus degradation	Others	117
Proteases released by the host
Aminopeptidase B	Human colonic tissues	Metalloprotease	Lysine-cleaving protease identified as active in CD	IBD	8
Cathepsin G	Human colonic tissue	Serine protease	Overactive	IBD	8
	Human stool		Epithelial barrier alteration	IBD	28
Dipeptidyl Peptidase-4	Human stool/intestinal tissue	Serine protease	Increased levels and expression	IBD	163
ELA 2A (Elastase 2A)	Human colonic cells	Serine protease	Epithelial barrier dysfunction	IBD	29
Thrombin	Human colonic tissue	Serine protease	Overactive	IBD	8
Trypsin-like, Elastase-like Cathepsin G-like Proteinase 3-like	Human stool	Serine proteases	Elevated activity	IBD	12
Kallikrein	Human intestinal tissue/stool	Serine protease	Inflammatory process in Crohn’s disease.	IBD/IBS	13,164
Trypsin-like Chymotrypsin-like Elastase-like	Human stool	Serine protease	Elevated in patients with high proteolytic activity	IBS	13
Trypsin-3/Trypsin-like activity	Human colonic tissue	Serine protease	Upregulated in intestinal epithelial, signal to enteric neurons and to induce visceral hypersensitivity/somatic and visceral hyperalgesia and allodynia in colon mice	IBS	7,58
Tryptase-alphabeta-1/Tryptase	Rat colonic tissue	Serine protease	Expression increased in colon of rats pots-colitis with visceral hypersensitivity/somatic and visceral hyperalgesia and allodynia in colon mice	IBS	31, 58

ND = Not determined