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1.
Dharmaprakash Viszwapriya Ganapathy Ashwinkumar Subramenium Solai Radhika Shunmugiah Karutha Pandian 《Antonie van Leeuwenhoek》2017,110(1):153-165
Streptococcus mutans, a multivirulent pathogen is considered the primary etiological agent in dental caries. Development of antibiotic resistance in the pathogen has created a need for novel antagonistic agents which can control the virulence of the organism and reduce resistance development. The present study demonstrates the in vitro anti-virulence potential of betulin (lup-20(29)-ene-3β,28-diol), an abundantly available plant triterpenoid against S. mutans UA159. Betulin exhibited significant dose dependent antibiofilm activity without affecting bacterial viability. At 240 µg/ml (biofilm inhibitory concentration), betulin inhibited biofilm formation and adherence to smooth glass surfaces by 93 and 71 % respectively. It reduced water insoluble glucan synthesis by 89 %, in conjunction with down regulation of gtfBC genes. Microscopic analysis confirmed the disruption in biofilm architecture and decreased exopolysaccharide production. Acidogenicity and aciduricity, key virulence factors responsible for carious lesions, were also notably affected. The induced auto-aggregation of cells upon treatment could be due to the down regulation of vicK. Results of gene expression analysis demonstrated significant down-regulation of virulence genes upon betulin treatment. Furthermore, the nontoxic effect of betulin on peripheral blood mononuclear cells even after 72 h treatment makes it a strong candidate for assessing its suitability to be used as a therapeutic agent. 相似文献
2.
Kim Vriens Tanne L. Cools Peta J. Harvey David J. Craik Pieter Spincemaille David Cassiman Annabel Braem Jozef Vleugels Peter H. Nibbering Jan Wouter Drijfhout Barbara De Coninck Bruno P. A. Cammue Karin Thevissen 《PloS one》2015,10(8)
Plant defensins are small, cysteine-rich peptides with antifungal activity against a broad range of yeast and fungi. In this study we investigated the antibiofilm activity of a plant defensin from coral bells (Heuchera sanguinea), i.e. HsAFP1. To this end, HsAFP1 was heterologously produced using Pichia pastoris as a host. The recombinant peptide rHsAFP1 showed a similar antifungal activity against the plant pathogen Fusarium culmorum as native HsAFP1 purified from seeds. NMR analysis revealed that rHsAFP1 consists of an α-helix and a triple-stranded antiparallel β-sheet stabilised by four intramolecular disulfide bonds. We found that rHsAFP1 can inhibit growth of the human pathogen Candida albicans as well as prevent C. albicans biofilm formation with a BIC50 (i.e. the minimum rHsAFP1 concentration required to inhibit biofilm formation by 50% as compared to control treatment) of 11.00 ± 1.70 μM. As such, this is the first report of a plant defensin exhibiting inhibitory activity against fungal biofilms. We further analysed the potential of rHsAFP1 to increase the activity of the conventional antimycotics caspofungin and amphotericin B towards C. albicans. Synergistic effects were observed between rHsAFP1 and these compounds against both planktonic C. albicans cells and biofilms. Most notably, concentrations of rHsAFP1 as low as 0.53 μM resulted in a synergistic activity with caspofungin against pre-grown C. albicans biofilms. rHsAFP1 was found non-toxic towards human HepG2 cells up to 40 μM, thereby supporting the lack of a general cytotoxic activity as previously reported for HsAFP1. A structure-function study with 24-mer synthetic peptides spanning the entire HsAFP1 sequence revealed the importance of the γ-core and its adjacent regions for HsAFP1 antibiofilm activity. These findings point towards broad applications of rHsAFP1 and its derivatives in the field of antifungal and antibiofilm drug development. 相似文献
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Poulomi Chakraborty Sutapa Joardar Shounak Ray Papu Biswas Debasish Maiti Prosun Tribedi 《Folia microbiologica》2018,63(6):763-772
Microbial biofilms are factions of surface-colonized cells encompassed in a matrix of extracellular polymeric substances. Profound application of antibiotics in order to treat infections due to microbial biofilm has led to the emergence of several drug-resistant microbial strains. In this context, a novel type of 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine (pytz)-capped silver nanoparticles (TzAgNPs) was synthesized, and efforts were given to test its antimicrobial and antibiofilm activities against Pseudomonas aeruginosa, a widely used biofilm-forming pathogenic organism. The synthesized TzAgNPs showed considerable antimicrobial activity wherein the MIC value of TzAgNPs was found at 40 μg/mL against Pseudomonas aeruginosa. Antibiofilm activity of TzAgNPs was also tested against Pseudomonas aeruginosa by carrying out an array of experiments like microscopic observation, crystal violet assay, and protein count using the sub-MIC doses of TzAgNPs. Since TzAgNPs showed efficient antibiofilm activity, thus, in the present study, efforts were put together to investigate the underlying cause of biofilm attenuation of Pseudomonas aeruginosa by using TzAgNPs. To this end, we discerned that the sub-MIC doses of TzAgNPs increased ROS level considerably in the bacterial cell. The result showed that the ROS level and microbial biofilm formation are inversely proportional. Thus, the attenuation in microbial biofilm could be attributed to the accumulation of ROS level. Furthermore, it was also duly noted that microorganisms upon treatment with TzAgNPs exhibited considerable diminution in virulence factors (protease and pyocyanin) in contrast to the control where the organisms were not treated with TzAgNPs. Thus, the results indicated that TzAgNPs exhibit considerable reduction in the development of biofilms and spreading of virulence factors. Taken together, all the results indicated that TzAgNPs could be deemed to be a promising agent for the prevention of microbial biofilm development that might assist to fight against infections linked to biofilm. 相似文献
5.
Duangkamol Kunthalert Sudarat Baothong Pichit Khetkam Suwadee Chokchaisiri Apichart Suksamrarn 《Microbiology and immunology》2014,58(10):581-589
Nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, frequently causes biofilm infections. Currently, resistance of bacteria within the biofilm to conventional antimicrobials poses a major obstacle to effective medical treatment on a global scale. Novel agents that are effective against NTHi biofilm are therefore urgently required. In this study, a series of natural and synthetic chalcones with various chemical substituents were evaluated in vitro for their antibiofilm activities against strong biofilm‐forming strains of NTHi. Of the test chalcones, 3‐hydroxychalcone (chalcone 8 ) exhibited the most potent inhibitory activity, its mean minimum biofilm inhibitory concentration (MBIC50) being 16 μg/mL (71.35 μM), or approximately sixfold more active than the reference drug, azithromycin (MBIC50 419.68 μM). The inhibitory activity of chalcone 8 , which is a chemically modified chalcone, appeared to be superior to those of the natural chalcones tested. Significantly, chalcone 8 inhibited biofilm formation by all studied NTHi strains, indicating that the antibiofilm activities of this compound occur across multiple strong‐biofilm forming NTHi isolates of different clinical origins. According to antimicrobial and growth curve assays, chalcone 8 at concentrations that decreased biofilm formation did not affect growth of NTHi, suggesting the biofilm inhibitory effect of chalcone 8 is non‐antimicrobial. In terms of structure–activity relationship, the possible substituent on the chalcone backbone required for antibiofilm activity is discussed. These findings indicate that 3‐hydroxychalcone (chalcone 8 ) has powerful antibiofilm activity and suggest the potential application of chalcone 8 as a new therapeutic agent for control of NTHi biofilm‐associated infections. 相似文献
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Beema Shafreen Raja Mohamed Muthamil Subramanian Karutha Pandian Shunmugiah 《Applied microbiology and biotechnology》2014,98(15):6775-6785
Candida albicans is an important opportunistic fungal pathogen, responsible for biofilm associated infections in immunocompromised patients. The aim of the present study was to investigate the antibiofilm properties of novel levofloxacin derivatives on C. albicans biofilms. The levofloxacin derivatives at their Biofilm Inhibitory Concentrations (BIC) were able to inhibit the biofilms of C. albicans, the yeast-to-hyphal transition and were also able to disrupt their mature biofilms. Furthermore, Real-time PCR analysis showed that the expression of ergosterol biosynthesis pathway gene (ERG11) and the efflux pump-encoding genes (CDR1 and MDR1) was decreased upon treatment with the levofloxacin derivatives. The total ergosterol content quantified using UV spectrophotomer showed decrease in ergosterol in the presence of levofloxacin derivatives. Overall, levofloxacin derivatives (6a, 6c and 7d) are capable of inhibiting C. albicans virulence factors. Therefore, these compounds with potential therapeutic implications can be used as new strategy to treat biofilm-related candidal infections. 相似文献
8.
Listeria monocytogenes is a Gram-positive bacterium, able to survive and grow in water, soil, agricultural products, various foods and the food-processing environment. The ubiquitous nature of the organism, coupled with its ability to colonise food-processing surfaces by forming biofilms, causes it to be of a major concern to the industry. Increased foodborne pathogen resistance and negative consumer perceptions regarding the use of synthetic bacteriocides, has resulted in natural antimicrobials being sourced from the plant kingdom. The listerial antibiofilm activities of Syzygium aromaticum (clove), Mentha spicata (spearmint), Lippia rehmannii and Cymbopogon citratus (lemongrass) essential oils and their major components were evaluated using the crystal violet assay and confocal scanning laser microscopy. Listerial biofilms treated with S. aromaticum or M. spicata essential oils, or the pure compounds nerol and citral, exhibited a similar biofilm biomass to the positive control. However, the essential oils of lemongrass, L. rehmannii, eugenol and R-carvone caused biofilm enhancement, rather than inhibition. L. rehmannii and lemongrass essential oils did not display any antibiofilm properties. Results obtained were confirmed by microscopic observations indicating either a reduction (inhibition) or an increase (enhancement) in biofilm biomass when exposed to the essential oils or pure compounds. The present study revealed that M. spicata and S. aromaticum essential oils as well as pure citral and nerol are good candidates for further development of ecofriendly disinfectants. 相似文献
9.
K. Murugan K. Selvanayaki Saleh Al-Sohaibani 《World journal of microbiology & biotechnology》2011,27(7):1661-1668
Respiratory tract and device associated infections caused by biofilm forming Pseudomonas aeruginosa play a primary role in the pathogenesis and prognosis of cystic fibrosis (CF) diseases. The biofilm formed by these pathogens
attributes to the antibiotic resistance and protection from host immune response. Once established, the pathogens respond
poorly to therapeutic agents. Recently medicinal plants are largely explored as potential source of bioactive agents. In this
context the present study reports the antibiofilm activity of the folkloric medicinal plant Andrographis paniculata against biofilm forming CF causative Pseudomonas aeruginosa isolated from CF sputum. P. aeruginosa was also assessed for their growth and development of the biofilm, phylogenetic relationship and antibiotic susceptibility.
Antibiogram of the strains indicated that they were resistant to more than one antibiotic. Six extracts of A. paniculata showed significant antibiofilm activity. P. aeruginosa strains, KMS P03 and KMS P05, were found to be maximally inhibited by the methanol extract to an extent of 88.6 and 87.5%
respectively. This is the first report on antibiofilm activity of A. paniculata extracts, and our results indicate scope for development of complementary medicine for biofilm associated infections. 相似文献
10.
《Phytomedicine》2021
BackgroundCandida albicans is one of the most common causative of opportunistic infections. Treatment of candidiasis is challenging considering the few antifungal drugs available and the increase in resistance. Antimicrobial photodynamic therapy (aPDT) is a recently developed therapeutic option that combines a non-toxic photosensitizer (PS) and light to kill the microbial pathogens. Targeting virulence, defined as the ability of a pathogen to cause overt disease, represents another attractive target for the development of novel antifungal agents. Thymophylla pentachaeta (DC.) Small var. belenidium (DC.) is an endemic plant from Argentina in which the presence of thiophenes, biologically active compounds whose antifungal activity is enhanced by irradiation with Ultraviolet A (UVA), have been already described.PurposeThe purpose of this study was to evaluate the photodynamic antifungal activity of hexane (Hex), dichloromethane (DCM), ethyl acetate (EtOAc) and methanol (MeOH) extracts from T. pentachaeta var. belenidium and their inhibitory effects on C. albicans virulence factors as well as biofilm formation and eradication.Study Design/MethodsAntifungal photodynamic activity of Hex, DCM, EtOAc and MeOH extracts from different parts of the plant were assessed with the microbroth dilution, bioautography and the time-kill assays, under light and darkness conditions. The capacities of the most active extracts of inhibiting Candida virulence factors (adherence to epithelial cells, germ tube and pseudomycelium formation and hydrolytic enzyme secretion) were assessed. In addition, the activity against biofilm formation and eradication has been investigated by reaction with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) that quantifies living cells in these structures.ResultsHex and DCM extracts from T. pentachaeta roots exhibited high photodynamic antifungal activity against C. albicans [Minimal fungicide concentrations (MFCs)= 7.8 µg/ml] under UVA light irradiation. Chemical analysis of active extracts (Hex and DCM from roots) revealed the presence of photoactive thiophenes. Both extracts generate reactive oxygen species through type I and II mechanisms. These extracts, at sub-inhibitory concentrations, under light conditions decreased the adherence of C. albicans to Buccal Epithelial Cells (BEC), inhibited germ tube formation and reduced esterase production. Finally, they demonstrated activity against preformed biofilms submitted to irradiation (MFCs= 3.91 µg/ml and 15.63 µg/ml for Hex and DCM extracts, respectively).ConclusionTaking together, results demonstrated the strong photodynamic effects of T. pentachaeta root extracts under UVA irradiation, making them valuable alternatives to the already established antifungal drugs against C. albicans. 相似文献
11.
Anjuli M. Timmer John C. Timmer Morgan A. Pence Li-Chung Hsu Mariam Ghochani Terrence G. Frey Michael Karin Guy S. Salvesen Victor Nizet 《The Journal of biological chemistry》2009,284(2):862-871
Group A Streptococcus (GAS) is a leading human bacterial pathogen
capable of producing invasive infections even in previously healthy
individuals. As frontline components of host innate defense, macrophages play
a key role in control and clearance of GAS infections. We find GAS induces
rapid, dose-dependent apoptosis of primary and cultured macrophages and
neutrophils. The cell death pathway involves apoptotic caspases, is partly
dependent on caspase-1, and requires GAS internalization by the phagocyte.
Analysis of GAS virulence factor mutants, heterologous expression, and
purified toxin studies identified the pore-forming cytolysin streptolysin O
(SLO) as necessary and sufficient for the apoptosis-inducing phenotype.
SLO-deficient GAS mutants induced less macrophage apoptosis in vitro
and in vivo, allowed macrophage cytokine secretion, and were less
virulent in a murine systemic infection model. Ultrastructural evidence of
mitochondrial membrane remodeling, coupled with loss of mitochondrial
depolarization and cytochrome c release, suggests a direct attack of
the toxin initiates the intrinsic apoptosis pathway. A general caspase
inhibitor blocked SLO-induced apoptosis and enhanced macrophage killing of
GAS. We conclude that accelerated, caspase-dependent macrophage apoptosis
induced by the pore-forming cytolysin SLO contributes to GAS immune evasion
and virulence.Group A Streptococcus
(GAS)4 is a leading
human pathogen that annually infects hundreds of millions of people worldwide
(1). The last 3 decades have
witnessed a marked increase in severe, invasive forms of GAS infection, many
attributable to a single globally disseminated clone of the M1T1 serotype
(2). Invasive GAS infection
defines a capacity of the pathogen to resist host innate defense mechanisms
designed to prevent microbial spread beyond epithelial surfaces.Macrophages are critical host defense cells involved directly in bacterial
clearance and also in alerting other immune system components to invading
pathogens. Macrophage microbicidal activity is accomplished by phagocytic
uptake coupled with the action of reactive oxygen species, enzymatic
proteolysis, and cationic antimicrobial peptides; their role in amplification
of the innate and adaptive immune responses is achieved through release of
soluble factors such as cytokines and nitric oxide. Mice depleted of
macrophages or treated with inhibitors of macrophage phagocytosis cannot clear
GAS infections even at relatively low challenge doses
(3), demonstrating the
essential first line defense function of these immune cells against the
pathogen.We sought to explore the interaction of the highly virulent GAS M1T1 clone
with macrophages to better understand its propensity to produce invasive human
infection. A prominent regulatory feature of macrophage biology in the context
of infectious disease and inflammation is the process of apoptosis, mediated
by caspase family proteases. Although a number of highly adapted intracellular
bacterial pathogens, including Mycobacterium tuberculosis, Legionella
pneumophila, and Brucella spp., have evolved mechanisms to block
macrophage apoptosis and use the host cell as a vehicle for in vivo
dissemination
(4–6),
a recent study of GAS M1T1 interactions with another host phagocytic cell type
suggested a different outcome. In contrast to other prominent Gram-positive
pathogens, including Staphylococcus aureus and Listeria
monocytogenes, GAS induced an accelerated program of apoptosis in human
neutrophils (7), although the
specific virulence factor(s) involved, effects on caspase activation, and
contribution to disease outcome were not studied.Here we report that GAS rapidly induces macrophage apoptosis through
caspase-dependent pathways, promoted by release of cytochrome c and
permeabilization of mitochondrial outer membranes. GAS-induced macrophage
apoptosis is mediated by the cytolysin streptolysin O (SLO), which is both
necessary and sufficient for the phenotype. SLO-mediated macrophage apoptosis
leads to enhanced GAS survival, dampened cytokine responses, and increased
virulence during systemic infection. 相似文献
12.
Paramasivam Nithyanand Ramalingam Thenmozhi Janarthanam Rathna Shunmugiah Karutha Pandian 《Current microbiology》2010,60(6):454-460
Streptococcus pyogenes biofilms tend to exhibit significant tolerance to antimicrobials during infections. We screened coral-associated actinomycetes
(CAA) for antibiofilm activity against different biofilm forming M serotype of Streptococcus pyogenes. Actinomycetes isolated from the mucus of the coral Acropora digitifera were screened for antibiofilm activity against S. pyogenes biofilms wherein several isolates clearly demonstrated antibiofilm activity. The biofilm inhibitory concentrations (BICs)
and the sub-BICs (1/2 and 1/4 BIC) of the extracts significantly prevented biofilm formation up to 60–80%. The extract of
Streptomyces akiyoshinensis (A3) displayed efficient antibiofilm activity against all the biofilm forming M serotypes. All the five extracts efficiently
reduced the cell surface hydrophobicity (a crucial factor for biofilm formation in S. pyogenes) of three M types and thus may inhibit biofilm formation. CAA represent an interesting source of marine invertebrates-derived
antibiofilm agents in the development of new strategies to combat Streptococcal biofilms. 相似文献
13.
Yibao Ma Yuanxi Xu Bryan D. Yestrepsky Roderick J. Sorenson Meng Chen Scott D. Larsen Hongmin Sun 《PloS one》2012,7(10)
Staphylococcus aureus is a major human pathogen and one of the more prominent pathogens causing biofilm related infections in clinic. Antibiotic resistance in S. aureus such as methicillin resistance is approaching an epidemic level. Antibiotic resistance is widespread among major human pathogens and poses a serious problem for public health. Conventional antibiotics are either bacteriostatic or bacteriocidal, leading to strong selection for antibiotic resistant pathogens. An alternative approach of inhibiting pathogen virulence without inhibiting bacterial growth may minimize the selection pressure for resistance. In previous studies, we identified a chemical series of low molecular weight compounds capable of inhibiting group A streptococcus virulence following this alternative anti-microbial approach. In the current study, we demonstrated that two analogs of this class of novel anti-virulence compounds also inhibited virulence gene expression of S. aureus and exhibited an inhibitory effect on S. aureus biofilm formation. This class of anti-virulence compounds could be a starting point for development of novel anti-microbial agents against S. aureus. 相似文献
14.
David Ermert Jutamas Shaughnessy Thorsten Joeris Jakub Kaplan Catherine J. Pang Evelyn A. Kurt-Jones Peter A. Rice Sanjay Ram Anna M. Blom 《PLoS pathogens》2015,11(7)
Streptococcus pyogenes, also known as Group A Streptococcus (GAS), is an important human bacterial pathogen that can cause invasive infections. Once it colonizes its exclusively human host, GAS needs to surmount numerous innate immune defense mechanisms, including opsonization by complement and consequent phagocytosis. Several strains of GAS bind to human-specific complement inhibitors, C4b-binding protein (C4BP) and/or Factor H (FH), to curtail complement C3 (a critical opsonin) deposition. This results in diminished activation of phagocytes and clearance of GAS that may lead to the host being unable to limit the infection. Herein we describe the course of GAS infection in three human complement inhibitor transgenic (tg) mouse models that examined each inhibitor (human C4BP or FH) alone, or the two inhibitors together (C4BPxFH or ‘double’ tg). GAS infection with strains that bound C4BP and FH resulted in enhanced mortality in each of the three transgenic mouse models compared to infection in wild type mice. In addition, GAS manifested increased virulence in C4BPxFH mice: higher organism burdens and greater elevations of pro-inflammatory cytokines and they died earlier than single transgenic or wt controls. The effects of hu-C4BP and hu-FH were specific for GAS strains that bound these inhibitors because strains that did not bind the inhibitors showed reduced virulence in the ‘double’ tg mice compared to strains that did bind; mortality was also similar in wild-type and C4BPxFH mice infected by non-binding GAS. Our findings emphasize the importance of binding of complement inhibitors to GAS that results in impaired opsonization and phagocytic killing, which translates to enhanced virulence in a humanized whole animal model. This novel hu-C4BPxFH tg model may prove invaluable in studies of GAS pathogenesis and for developing vaccines and therapeutics that rely on human complement activation for efficacy. 相似文献
15.
Diane Ly Deborah Donahue Mark J. Walker Victoria A. Ploplis Jason D. McArthur Marie Ranson Francis J. Castellino Martina L. Sanderson-Smith 《Microbes and infection / Institut Pasteur》2019,21(8-9):412-417
Plasmin(ogen) acquisition is critical for invasive disease initiation by Streptococcus pyogenes (GAS). Host urokinase plasminogen activator (uPA) plays a role in mediating plasminogen activation for GAS dissemination, however the contribution of tissue-type plasminogen activator (tPA) to GAS virulence is unknown. Using novel tPA-deficient ALBPLG1 mice, our study revealed no difference in mouse survival, bacterial dissemination or the pathology of GAS infection in the absence of tPA in AlbPLG1/tPA?/? mice compared to AlbPLG1 mice. This study suggests that tPA has a limited role in this humanized model of GAS infection, further highlighting the importance of its counterpart uPA in GAS disease. 相似文献
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Kelei Zhao Yongqiang Tian Bisong Yue Hongning Wang Xiuyue Zhang 《Archives of microbiology》2013,195(3):203-209
Trueperella pyogenes (formerly Arcanobacterium) is commonly isolated from domesticated or wild ruminants as an opportunistic pathogen. To investigate the role of virulence determinants (VDs) and biofilm production in T. pyogenes isolates, a total of 36 T. pyogenes were collected from abscesses of forest musk deer in Miyaluo Farm (Sichuan Province, China). The prevalence of VDs and associations with clonal types, antibiotic resistance and biofilm production were analyzed by PCR and bioassay. Finally, T. pyogenes isolates were separated into three clonal types based on the DNA fingerprinting of BOX-PCR. Isolates with less VDs obtained from sick forest musk deer were mainly belonged to Type 1, and the isolates with robust VD repertoire obtained from dead forest musk deer were included in Type 3. Accordingly, resistant isolates exhibited significant lower virulence than susceptible ones. Majority of T. pyogenes isolates of this study were capable of producing a biofilm. However, no VDs presence and antibiotic resistance were statistically associated with biofilm production. In conclusion, the current study demonstrated that T. pyogenes was probably the primary pathogen of abscesses in the forest musk deer. Moreover, as an animal origin pathogen, the increasing resistance of T. pyogenes isolates could also associate with a decreased virulence. 相似文献
19.
The Streptococcus pyogenes orphan protein tyrosine phosphatase,SP‐PTP,possesses dual specificity and essential virulence regulatory functions
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Sashi Kant Shivani Agarwal Preeti Pancholi Vijay Pancholi 《Molecular microbiology》2015,97(3):515-540
Group A Streptococcus (GAS) is a human pathogen that causes high morbidity and mortality. GAS lacks a gene encoding tyrosine kinase but contains one encoding tyrosine phosphatase (SP‐PTP). Thus, GAS is thought to lack tyrosine phosphorylation, and the physiological significance of SP‐PTP is, therefore, questionable. Here, we demonstrate that SP‐PTP possesses dual phosphatase specificity for Tyr‐ and Ser/Thr‐phosphorylated GAS proteins, such as Ser/Thr kinase (SP‐STK) and the SP‐STK‐phosphorylated CovR and WalR proteins. Phenotypic analysis of GAS mutants lacking SP‐PTP revealed that the phosphatase activity per se positively regulates growth, cell division and the ability to adhere to and invade host cells. Furthermore, A549 human lung cells infected with GAS mutants lacking SP‐PTP displayed increased Ser‐/Thr‐/Tyr‐phosphorylation. SP‐PTP also differentially regulates the expression of ~50% of the total GAS genes, including several virulence genes potentially through the two‐component regulators, CovR, WalR and PTS/HPr regulation of Mga. Although these mutants exhibit attenuated virulence, a GAS mutant overexpressing SP‐PTP is hypervirulent. Our study provides the first definitive evidence for the presence and importance of Tyr‐phosphorylation in GAS and the relevance of SP‐PTP as an important therapeutic target. 相似文献