Salmonella can invade non-phagocytic cells through its type Ⅲ secretion system （T3SS-1）, which induces a Trigger entry process. This study showed that Salmonella enterica, subspecies enterica serovar Enteritidis ca...Salmonella can invade non-phagocytic cells through its type Ⅲ secretion system （T3SS-1）, which induces a Trigger entry process. This study showed that Salmonella enterica, subspecies enterica serovar Enteritidis can also invade cells via the Rck outer membrane protein. Rck was necessary and sufficient to enable non-invasive E. coli and Rckcoated beads to adhere to and invade different cells. Internalization analysis of latex beads coated with different Rck peptides showed that the peptide containing amino acids 140-150 promoted adhesion, whereas amino acids between 150 and 159 modulated invasion. Expression of dominant-negative derivatives and use of specific inhibitors demonstrated the crucial role of small GTPases Racl and Cdc42 in activating the Arp2/3 complex to trigger formation of actin-rich accumulation, leading to Rck-dependent internalization. Finally, scanning and transmission electron microscopy with Rck-coated beads and E. coli expressing Rck revealed microvillus-like extensions that formed a Zipper-like structure, engulfing the adherent beads and bacteria. Overall, our results provide new insights into the Salmonella T3SS-independent invasion mechanisms and strongly suggest that Rck induces a Zipper-like entry mechanism. Consequently, Salmonella seems to be the first bacterium found to be able to induce both Zipper and Trigger mechanisms to invade host cells.展开更多
BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.Howe...BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.展开更多
文摘Salmonella can invade non-phagocytic cells through its type Ⅲ secretion system （T3SS-1）, which induces a Trigger entry process. This study showed that Salmonella enterica, subspecies enterica serovar Enteritidis can also invade cells via the Rck outer membrane protein. Rck was necessary and sufficient to enable non-invasive E. coli and Rckcoated beads to adhere to and invade different cells. Internalization analysis of latex beads coated with different Rck peptides showed that the peptide containing amino acids 140-150 promoted adhesion, whereas amino acids between 150 and 159 modulated invasion. Expression of dominant-negative derivatives and use of specific inhibitors demonstrated the crucial role of small GTPases Racl and Cdc42 in activating the Arp2/3 complex to trigger formation of actin-rich accumulation, leading to Rck-dependent internalization. Finally, scanning and transmission electron microscopy with Rck-coated beads and E. coli expressing Rck revealed microvillus-like extensions that formed a Zipper-like structure, engulfing the adherent beads and bacteria. Overall, our results provide new insights into the Salmonella T3SS-independent invasion mechanisms and strongly suggest that Rck induces a Zipper-like entry mechanism. Consequently, Salmonella seems to be the first bacterium found to be able to induce both Zipper and Trigger mechanisms to invade host cells.
基金Supported by the Shandong Provincial Natural Science Foundation of China,No.ZR2023QH015Qingdao Municipal Natural Science Foundation of China,No.23-2-1-134-zyyd-jch.
文摘BACKGROUND Protein-losing enteropathy(PLE)is a rare cause of hypoalbuminemia that can be attributed to intestinal lymphangiectasia.Patients with Noonan syndrome may present with disorder of lymph vessel formation.However,PLE is rarely reported with Noonan syndrome.CASE SUMMARY A 15-year-old female was hospitalized multiple times for recurrent edema and diarrhea secondary to hypoalbuminemia.Additional manifestations included a ventricular septal defect at birth,intermuscular hemangioma,slightly wide interocular and intermammary distances,and absence of the distal phalanx of the left little finger since birth.Abdominal computed tomography revealed cavernous transformation of the portal vein,and liver biopsy indicated“porto-sinusoidal vascular disease”.Whole exome and Sanger sequencing revealed a heterozygous mutation(exon9:C.850C>T:P.R284C)in leucine zipper-like transcription regulator 1,suggesting Noonan syndrome type 10.Further examinations revealed thoracic duct dysplasia and intestinal lymphangiectasia causing PLE in this patient.A multidisciplinary team decided to address thoracic duct dysplasia with outlet obstruction.Approximately two years after the microsurgical relief of the thoracic duct outlet obstruction,the patient achieved persistent normal serum albumin level without edema or diarrhea.Furthermore,the relevant literatures on Noonan syndrome and PLE were reviewed.CONCLUSION Herein,we reported the first case of PLE associated with Noonan syndrome caused by a rare genetic mutation in leucine zipper-like transcription regulator 1(c.850C>T:P.R284C)with newly reported manifestations.This case presented the successful treatment of clinical hypoalbuminemia attributed to thoracic duct dysplasia,intestinal lymphangiectasia and PLE.
