scholarly journals Elucidation of the genetic mechanisms contributing to moenomycin resistance in actinobacteria

2018 ◽  
Vol 22 ◽  
pp. 203-209
Author(s):  
B. O. Ostash ◽  
O. S. Yushchuk ◽  
O. T. Koshla ◽  
Y. Rebets ◽  
I. S. Ostash ◽  
...  

Aim. Moenomycins are phosphoglycolipid antibiotics produced almost exclusively by representatives of genus Streptomyces. These antibiotics directly inhibit peptidoglycan glycosyltransferases and are extremely active against cocci. Here we studied how antibiotic-producing actinobacteria protect themselves from toxic action of moenomycins. Methods. Microbiological and molecular genetic approaches were combined to reveal intrinsic levels and distribution of moenomycin resistance across actinobacteria genera, and to pinpoint genes contributing to moenomycin resistance in model strain Streptomyces coelicolor M145. Results. Out of 51 actinobacterial species (90 % of which Streptomyces) being tested, only Streptomyces albus J1074 turned out to be highly susceptible to moenomycin A, although resistant variants can be facilely raised. Several classes of mutations increased level of susceptibility of S. coelicolor to moenomycin, although in no case the latter was equal to what we observed in J1074 strain. Conclusions. Moenomycin resistance is widespread across actinobacteria, and it most likely is caused by a combination factors, such as richly decorated cell wall and organization of divisome apparatus. It is possible that moenomycin resistance mechanisms operating in actinobacteria and pathogenic cocci are different. Keywords: moenomycin, antibiotic resistance, peptidoglycan.

2017 ◽  
Vol 11 (2) ◽  
pp. 62-69
Author(s):  
Esraa Gh. Al-Sammak

يهدف البحث الى تسليط الضوء على دور التصنيف المتعدد Polyphasic والذي يضم كل من التصنيف المظهري والجيني لتحديد وتثبيت صفات النوع ضمن جنس الـStreptomyces   الصعب التصنيف نتيجة كثرة الانواع والتغاير الكبير في الصفات المظهرية اضافة لدورها في مجالات عدة منها البيئة من خلال تحملها العديد من املاح العناصرالثقيلة الموجودة في البيئات الملوثة بالهيدروكاربونات واشتراكها في التخلص من الملوثات. تم عزل وتشخيص ست  عزلات من البكتريا الخيطية  التابعة لجنس Streptomyces من عشرين عينة تربة ملوثة بالهيدروكاربونات وترب حدائق .  شخصت الى ثلاثة انواع اعتمادا على دراسة الصفات المظهرية والجينية من خلال دراسة تتابع جزء الـ16SrDNA باستخدام البادئ 27f  و 1392r  وشخصت سلالتين على انها تابعة للنوع     Streptomyces flavogriseus ATCC 33331 وسلالتين للنوع Streptomyces coelicolor A3(2) واخيرا سلالتين تابعة للنوع  Streptomyces albus J1074  . اعتمادا على الصفات المظهرية والبالغة 48 صفة  و باستخدام التصنيف العددي والربط باستخدام المعدل الموزون و معامل التشابه البسيط Simple matching coefficient (Ssm)  باستخدام البرنامج الاحصائي SPSS  , تعنقدت السلالات في ثلاثة عناقيد ضمن المخطط الشجري ضم  العنقود A سلالتين للنوعStreptomyces coelicolor   مرتبطة عند نسبة تشابه 99%  في حين تعنقدت سلالتي النوع Streptomyces albus  ضمن العنقود B  وعند نسبة تشابه 95% كما تعنقدت سلالتي النوع Streptomyces flavogriseus  ضمن العنقود C  وبنسبة تشابه 95% . اظهرت الانواع المعزولة مستعمرات طباشيرية رصاصية الى بيضاء وتميز الغزل الهوائي للنوع   Streptomyces albus بكونه حلزوني مكبوس متفرع وكثيف في حين تميز بكون خيوط الغزل الهوائي متعرج وغير متفرع للنوع  Streptomyces flavogriseus وظهر الغزل الهوائي للنوع  Streptomyces coelicolor متفرع متحلزن ومتعرج و جميعها منتجة لرائحة  التربة. اظهرت جميع الانواع قيد الدراسة حساسية  لاملاح كل من كلوريد وكبريتات الزئبق , في حين اظهرت جميع الانواع مقاومة لكل من كلوريد ونترات الكوبلت و كبريتات الزنك و نترات  وخلات الرصاص و كبريتات النيكل و خلات الفضة وثنائي اوكسيد التيتانيوم . اعطت جميع الانواع حساسية للمضاد الحيوي,Ciprofloxacin  10 مايكروغرام  , 10 Tobramycinمايكروغرام  ,  Gentamicin  10 مايكروغرام , Vancomycin 30 مايكروغرام , Amikacin10مايكروغرام, Imipenem 10مايكروغرام. كما  تعنقدت الانواع ايضا عند استخدام التصنيف الجيني الى ثلاثة عناقيد  ضمن الشجرة  التطورية وبنسب تشابه تراوحت بين  96.7- 99.4  %باستخدام  Clustal W  وطريقة maximum likelihood method  باستخدام برنامج Mega 5.


Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 304
Author(s):  
Cheewin Kittikunapong ◽  
Suhui Ye ◽  
Patricia Magadán-Corpas ◽  
Álvaro Pérez-Valero ◽  
Claudio J. Villar ◽  
...  

Streptomyces albus J1074 is recognized as an effective host for heterologous production of natural products. Its fast growth and efficient genetic toolbox due to a naturally minimized genome have contributed towards its advantage in expressing biosynthetic pathways for a diverse repertoire of products such as antibiotics and flavonoids. In order to develop precise model-driven engineering strategies for de novo production of natural products, a genome-scale metabolic model (GEM) was reconstructed for the microorganism based on protein homology to model species Streptomyces coelicolor while drawing annotated data from databases and literature for further curation. To demonstrate its capabilities, the Salb-GEM was used to predict overexpression targets for desirable compounds using flux scanning with enforced objective function (FSEOF). Salb-GEM was also utilized to investigate the effect of a minimized genome on metabolic gene essentialities in comparison to another Streptomyces species, S. coelicolor.


Author(s):  
O. Rydkin ◽  
◽  
O. Koshla ◽  
B. Ostas ◽  
◽  
...  

Streptomyces albus J1074 has been established by us as a convenient model to study different aspects of tRNALeuUAA-dependent regulatory mechanisms, that take place in genus Streptomyces. These mechanisms are important for proper morphological and physiological transitions of streptomycete colonies, such as the onset of antibiotic production in stationary phase of growth. The genes for post-transcriptional modification of adenosine residue in 37th position of tRNAXXA family (so called mia genes) were shown to be important for the aforementioned processes, most likely because they impact tRNALeuUAA among other tRNAs. Our results were largely consistent with what is known about mia mutations in the other model systems, such as yeast and enterobacteria. Nevertheless, we also revealed several differences from the model systems, such as decreased susceptibility to hydrogen peroxide. This prompted us to look deeper into the behavior of the mia mutants, particularly their response to different stress factors. Here we report that S. albus mia mutants exhibit increased mistranslation rate as compared to their parental strain. These mutants are more susceptible than the parental strain to disulfide stress inducer diamide and DNA repair stressor caffeine. In summary, although the deficiency in certain tRNA modification appears to cause identical or very similar response (such as elevated mistranslation) across all so far studied bacterial systems, it also induces species- or genus-specific effects (such as disparate effects on H2O2 susceptibility). These differences could be attributed to the peculiarities of organization/function of regulatory pathway governing the response to a given stress. The observed results are further discussed in the wider context of the role of tRNA modification pathway in bacterial biology.


Marine Drugs ◽  
2018 ◽  
Vol 16 (8) ◽  
pp. 259 ◽  
Author(s):  
Raúl García-Salcedo ◽  
Rubén Álvarez-Álvarez ◽  
Carlos Olano ◽  
Librada Cañedo ◽  
Alfredo Braña ◽  
...  

Jomthonic acids (JAs) are a group of natural products (NPs) with adipogenic activity. Structurally, JAs are formed by a modified β-methylphenylalanine residue, whose biosynthesis involves a methyltransferase that in Streptomyces hygroscopicus has been identified as MppJ. Up to date, three JA members (A–C) and a few other natural products containing β-methylphenylalanine have been discovered from soil-derived microorganisms. Herein, we report the identification of a gene (jomM) coding for a putative methyltransferase highly identical to MppJ in the chromosome of the marine actinobacteria Streptomyces caniferus GUA-06-05-006A. In its 5’ region, jomM clusters with two polyketide synthases (PKS) (jomP1, jomP2), a nonribosomal peptide synthetase (NRPS) (jomN) and a thioesterase gene (jomT), possibly conforming a single transcriptional unit. Insertion of a strong constitutive promoter upstream of jomP1 led to the detection of JA A, along with at least two novel JA family members (D and E). Independent inactivation of jomP1, jomN and jomM abolished production of JA A, JA D and JA E, indicating the involvement of these genes in JA biosynthesis. Heterologous expression of the JA biosynthesis cluster in Streptomyces coelicolor M1152 and in Streptomyces albus J1074 led to the production of JA A, B, C and F. We propose a pathway for JAs biosynthesis based on the findings here described.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 164 ◽  
Author(s):  
Nikita Zrelovs ◽  
Viktorija Kurbatska ◽  
Zhanna Rudevica ◽  
Ainars Leonchiks ◽  
Davids Fridmanis

Rapid spread of antibiotic resistance throughout the kingdom bacteria is inevitably bringing humanity towards the “post-antibiotic” era. The emergence of so-called “superbugs”—pathogen strains that develop resistance to multiple conventional antibiotics—is urging researchers around the globe to work on the development or perfecting of alternative means of tackling the pathogenic bacteria infections. Although various conceptually different approaches are being considered, each comes with its advantages and drawbacks. While drug-resistant pathogens are undoubtedly represented by both Gram(+) and Gram(−) bacteria, possible target spectrum across the proposed alternative approaches of tackling them is variable. Numerous anti-virulence strategies aimed at reducing the pathogenicity of target bacteria rather than eliminating them are being considered among such alternative approaches. Sortase A (SrtA) is a membrane-associated cysteine protease that catalyzes a cell wall sorting reaction by which surface proteins, including virulence factors, are anchored to the bacterial cell wall of Gram(+) bacteria. Although SrtA inhibition seems perspective among the Gram-positive pathogen-targeted antivirulence strategies, it still remains less popular than other alternatives. A decrease in virulence due to inactivation of SrtA activity has been extensively studied in Staphylococcus aureus, but it has also been demonstrated in other Gram(+) species. In this manuscript, results of past studies on the discovery of novel SrtA inhibitory compounds and evaluation of their potency were summarized and commented on. Here, we discussed the rationale behind the inhibition of SrtA, raised some concerns on the comparability of the results from different studies, and touched upon the possible resistance mechanisms as a response to implementation of such therapy in practice. The goal of this article is to encourage further studies of SrtA inhibitory compounds.


2020 ◽  
Vol 63 (9) ◽  
pp. 1-4
Author(s):  
Jun Tian ◽  
Leixin Ye ◽  
Yuling Yang ◽  
Yalin Zhang ◽  
Changhua Hu ◽  
...  

2013 ◽  
Vol 57 (9) ◽  
pp. 4470-4480 ◽  
Author(s):  
Min Jung Kwun ◽  
Gabriela Novotna ◽  
Andrew R. Hesketh ◽  
Lionel Hill ◽  
Hee-Jeon Hong

ABSTRACTVanRS two-component regulatory systems are key elements required for the transcriptional activation of inducible vancomycin resistance genes in bacteria, but the precise nature of the ligand signal that activates these systems has remained undefined. Using the resistance system inStreptomyces coelicoloras a model, we have undertaken a series ofin vivostudies which indicate that the VanS sensor kinase in VanB-type resistance systems is activated by vancomycin in complex with thed-alanyl-d-alanine (d-Ala-d-Ala) termini of cell wall peptidoglycan (PG) precursors. Complementation of an essentiald-Ala-d-Ala ligase activity by constitutive expression ofvanAencoding a bifunctionald-Ala-d-Ala andd-alanyl-d-lactate (d-Ala-d-Lac) ligase activity allowed construction of strains that synthesized variable amounts of PG precursors containingd-Ala-d-Ala. Assays quantifying the expression of genes under VanRS control showed that the response to vancomycin in these strains correlated with the abundance ofd-Ala-d-Ala-containing PG precursors; strains producing a lower proportion of PG precursors terminating ind-Ala-d-Ala consistently exhibited a lower response to vancomycin. Pretreatment of wild-type cells with vancomycin or teicoplanin to saturate and mask thed-Ala-d-Ala binding sites in nascent PG also blocked the transcriptional response to subsequent vancomycin exposure, and desleucyl vancomycin, a vancomycin analogue incapable of interacting withd-Ala-d-Ala residues, failed to inducevangene expression. Activation of resistance by a vancomycin–d-Ala-d-Ala PG complex predicts a limit to the proportion of PG that can be derived from precursors terminating ind-Ala-d-Lac, a restriction also enforced by the bifunctional activity of the VanA ligase.


1952 ◽  
Vol 96 (6) ◽  
pp. 569-580 ◽  
Author(s):  
Maclyn McCarty

Cell wall preparations of uniform chemical constitution have been obtained from several strains of group A streptococci. The isolated cell walls are dissolved by the same fractions of the Streptomyces albus enzymes that are effective in the lysis of intact cells, and it is likely that enzymatic lysis of group A streptococci is effected by an attack on the cell wall. The streptococcal cell wall, as prepared in this study, consists of approximately two-thirds carbohydrate and one-third protein. Small amounts of other components may be present. The carbohydrate component, which is composed primarily of N-acetyl-glucosamine and rhamnose, is the group-specific C carbohydrate. The evidence indicates that one of the streptomyces enzymes is directed toward the carbohydrate component of the cell wall.


2019 ◽  
Vol 53 (1) ◽  
pp. 1-7 ◽  
Author(s):  
O. T. Koshla ◽  
I. V. Rokytskyy ◽  
I. S. Ostash ◽  
T. Busche ◽  
J. Kalinowski ◽  
...  

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