The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae

Objectives Alterations in the PhoPQ two-component regulatory system may be associated with colistin resistance in Klebsiella pneumoniae. MgrB is a small transmembrane protein produced upon activation of the PhoPQ signalling system, and acts as a negative regulator on this system. We investigated the role of the MgrB protein as a source of colistin resistance in a series of K. pneumoniae.Methods Colistin-resistant K. pneumoniae isolates were recovered from hospitalized patients worldwide (France, Turkey, Colombia and South Africa). The mgrB gene was amplified and sequenced. A wild-type mgrB gene was cloned and the corresponding recombinant plasmid was used for complementation assays. Clonal diversity was evaluated by MLST and Diversilab analysis.Results Of 47 colistin-resistant isolates, 12 were identified as having a mutated mgrB gene. Five clonally unrelated isolates had an mgrB gene truncated by an IS5-like IS, while one clone also harboured an insertional inactivation at the exact same position of the mgrB gene, but with ISKpn13. Another clone harboured an insertional inactivation due to ISKpn14 at another location of the mgrB gene. Two clonally related isolates harboured an IS (IS10R) in the promoter region of mgrB. Finally, three clonally unrelated isolates harboured substitutions leading to anticipated stop codon in the MgrB protein. Complementation assays with a wild-type MgrB protein restored full susceptibility to colistin for all colistin-resistant isolates identified with qualitative or quantitative MgrB modifications.Conclusion The inactivation or down-regulation of the mgrB gene was shown to be a source of colistin resistance in K. pneumoniae. Interestingly, identical genetic events were identified among clonally unrelated isolates

The mgrB gene as a key target for acquired resistance to colistin in Klebsiella pneumoniae

Objectives Alterations in the PhoPQ two-component regulatory system may be associated with colistin resistance in Klebsiella pneumoniae. MgrB is a small transmembrane protein produced upon activation of the PhoPQ signalling system, and acts as a negative regulator on this system. We investigated the role of the MgrB protein as a source of colistin resistance in a series of K. pneumoniae. Methods Colistin-resistant K. pneumoniae isolates were recovered from hospitalized patients worldwide (France, Turkey, Colombia and South Africa). The mgrB gene was amplified and sequenced. A wild-type mgrB gene was cloned and the corresponding recombinant plasmid was used for complementation assays. Clonal diversity was evaluated by MLST and Diversilab analysis. Results Of 47 colistin-resistant isolates, 12 were identified as having a mutated mgrB gene. Five clonally unrelated isolates had an mgrB gene truncated by an IS5-like IS, while one clone also harboured an insertional inactivation at the exact same position of the mgrB gene, but with ISKpn13. Another clone harboured an insertional inactivation due to ISKpn14 at another location of the mgrB gene. Two clonally related isolates harboured an IS (IS10R) in the promoter region of mgrB. Finally, three clonally unrelated isolates harboured substitutions leading to anticipated stop codon in the MgrB protein. Complementation assays with a wild-type MgrB protein restored full susceptibility to colistin for all colistin-resistant isolates identified with qualitative or quantitative MgrB modifications. Conclusion The inactivation or down-regulation of the mgrB gene was shown to be a source of colistin resistance in K. pneumoniae. Interestingly, identical genetic events were identified among clonally unrelated isolate

Pulmonary Involvement of Diffuse Large B-cell Lymphoma with Cavitary Lesions

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most common type of extranodal lymphoma. Typically disease occurs fastly growing nodal or extranodal masses with systemic symptoms. Pulmonary involvement may also occur in DLBCL. Here we present a DLBCL with cavitary lesions in the lung. A 59-year-old male was diagnosed with DLBCL through an endoscopic gastric biopsy that was performed 1.5 years ago. After six course of R-CHOP chemotherapy, the relaps of disease was confirmed with mediastinoscopy. Despite two courses of RICE chemotherapy and one course of R-BAB therapies, the patient was admitted to the intensive care unit with shortness of breath and tachypnea. Thorax computed tomography showed a mass lesion that enclosed and narrowed the right major bronchus and multiple lesions with cavitation. The infections were excluded with bronchoscopy. The patient received pulse steroid therapy, radiotherapy and three courses of Hyper-CVAD chemotherapy. In the control thorax CT, cavitary lesions got smaller, respiratory insufficiency of patient improved. When pulmonary cavitary lesions are observed in patients under follow-up with the diagnosis of lymphoma, the pulmonary involvement of lymphoma should also be considered in addition to the infectious agents

A Rare Cause of Cavitary Lesion in the Lung: Richter's Transformation.

Richter's transformation (RT) refers to the development of aggressive lymphoma during the course of CLL. Clinically, patients with RT present with an aggressive disease course with rapidly enlarging lymph nodes, hepatosplenomegaly, and elevated serum lactate dehydrogenase levels. But rarely it presents with extra nodal organ involvement at the beginning. Common sites of extra nodal involvement are the gastrointestinal tract, eye, central nervous system, lung, and kidney. We are reporting this case that was presented with RT in the lung involvement diagnosed while researching cavitary lesion etiology