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Background: Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. Methods: This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015–December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015–December 2019), along with those during the post-COVID-19 period (January–December 2020) were analyzed and compared. Results: A total of 6899 throat swab samples were collected during the pre-pandemic period of 2015–2019, with 2681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p

Abstract Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0–18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996–December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008–2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996–2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1–RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008–2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008–2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008–2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents’ use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Background/purpose: Antimicrobial resistance in Taiwan has been on the rise for two decades. The implementation of pneumococcal conjugate vaccination (PCV13) and enhanced antimicrobial control (2013–2015) by the government may have changed the antibiotic resistance. Methods: Four respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Moraxella catarrhalis) isolated in a single medical center during 2008–2017 were studied. We defined three temporal stages: (a) the first era (2008–2012), prior to implementation of the national immunization program (PCV13 vaccination), (b) the second era (2013–2015), during which an enhanced antibiotic control strategy was implemented, and (c) the third era (2016–2017), after implementation. Antimicrobial drug sensitivities were collected from two other hospitals: one from east Taiwan, one from west-central Taiwan. Results: S. pneumoniae was frequently isolated during the first era. It declined progressively during the second era of PCV13 vaccination. S. pyogenes and M. catarrhalis were not frequently isolated. The drug susceptibility of S. pneumoniae to ceftriaxone and vancomycin remained high. The antimicrobial susceptibility of H. influenzae to amoxillin/clavulante declined over the three temporal stages, from 91.9%-79.5%–58.5% (all p

Background: Enterovirus-D68 (EV-D68) has been endemic in Taiwan for some years with a small number of positive cases. Detailed information about respiratory presentation is lacking. This study characterized the clinical course in children admitted to the medical center and regional hospital in Taichung during 2015. Methods: Retrospective chart review of patients with confirmed EV-D68 infection admitted to the medical center and regional hospital in Taichung with respiratory symptoms in the second half of 2015. Past medical history, clinical presentation, management, and course in hospital were collected and analyzed. Simple demographic data and clinical symptoms were also collected from patients confirmed with EV-D68 infection who visited clinics in Taichung. Results: Six children were included. Two patients had a prior history of asthma or recurrent dyspnea, and one had other preexisting medical comorbidities. One child was admitted to the pediatric intensive care unit. All the patients were cured. Cough, rhinorrhea, tachypnea and fever were the most common clinical symptoms among inpatients, while influenza-like illness (ILI) was prevalent in outpatients. Conclusion: EV-D68 infection resulted in respiratory presentations of asthma-like illness in the hospitalized pediatric population. Patients with a prior history of asthma or recurrent dyspnea appear to be more severely affected. Key Words: enterovirus D68, respiratory presentation, taiwan

Background: Acute heart failure (AHF) is the major cause of death in children with severe enterovirus 71 (EV71) infection. This study aimed to report our clinical experience with EV71-related AHF, as well as to discuss its pathogenesis and relationship to Takotsubo syndrome (TTS).Methods: A total 27 children with EV71-related AHF between 1998 and 2018 were studied. The TTS diagnosis was based on the International Takotsubo Diagnostic Criteria.Results: Acute heart failure-related early death occurred in 10 (37%) of the patients. Sinus tachycardia, systemic hypertension, and pulmonary edema in 100, 85, and 81% of the patients, respectively, preceded AHF. Cardiac biomarkers were significantly increased in most patients. The main echocardiographic findings included transient and reversible left ventricular (LV) regional wall motion abnormality (RWMA) with apical ballooning. High concentrations of catecholamines either preceded or coexisted with AHF. Myocardial pathology revealed no evidence of myocarditis, which was consistent with catecholamine-induced cardiotoxic damage. Patients with EV71-related AHF who had received close monitoring of their cardiac function, along with early intervention involving extracorporeal life support (ECLS), had a higher survival rate (82 vs. 30%, p = 0.013) and better neurological outcomes (59 vs. 0%, p = 0.003).Conclusion: EV 71-related AHF was preceded by brain stem encephalitis-related hypercatecholaminemia, which resulted in a high mortality rate. Careful monitoring is merited so that any life-threatening cardiogenic shock may be appropriately treated. In view of the similarities in their clinical manifestations, natural course direction, pathological findings, and possible mechanisms, TTS and EV71-related AHF may represent the same syndrome. Therefore, we suggest that EV71-related AHF could constitute a direct causal link to catecholamine-induced secondary TTS.

Background/purpose: Staphylococcus aureus (S. aureus) causes diseases ranging from mild skin infections to invasive diseases. Carriage of S. aureus, including methicillin-resistant S. aureus (MRSA), is a significant risk factor for subsequent staphylococcal infection. Several studies discussed MRSA colonization in Taiwan, but mostly in northern Taiwan. This is the first study that estimates the prevalence of MRSA nasal colonization in healthy children and identifies the potential risk factors in central Taiwan. Methods: A total of 3144 healthy children aged 2–60 months who visited Taichung Veterans General Hospital (TCVGH) were screened for nasal S. aureus carriage from July 2005 to December 2010. Questionnaires included demographic information and potential risk factors for carriage of S. aureus were completed by parents/guardians. Results: Prevalence of MSSA and MRSA were 12.09% and 5.25%, respectively. The youngest group aged 2–6 months had the highest S. aureus carriage rate, and the carriage rate revealed a peak in summer. The nasal colonization of Streptococcus pneumoniae (S. pneumoniae) was a protective factor against S. aureus colonization. 85% of the MRSA colonizing isolates belonged to clonal complex 59/staphylococcal cassette chromosome type IV or VT, the local community clone in Taiwan. Conclusion: An increasing trend of MRSA nasal carriage rate in Taiwan had been brought forward, however, it was not observed in central Taiwan during the period of 2005–2010. We found a summer peak on both MRSA and MSSA carriages. Keywords: Central Taiwan, Children, Methicillin-resistant Staphylococcus aureus colonization

Background: Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an excessive number of immature lymphocytes, including immature precursors of both B- and T cells. ALL affects children more often than adults. Immature lymphocytes lead to arrested differentiation and proliferation of cells. Its conventional treatments involve medication with dexamethasone, vincristine, and other anticancer drugs. Although the current first-line drugs can achieve effective treatment, they still cannot prevent the recurrence of some patients with ALL. Treatments have high risk of recurrence especially after the first remission. Currently, novel therapies to treat ALL are in need. Autophagy and apoptosis play important roles in regulating cancer development. Autophagy involves degradation of proteins and organelles, and apoptosis leads to cell death. These phenomena are crucial in cancer progression. Past studies reported that many potential anticancer agents regulate intracellular signaling pathways. Methods: The authors discuss the recent research findings on the role of autophagy and apoptosis in ALL. Results: The autophagy and apoptosis are widely used in the treatment of ALL. Most studies showed that many agents regulate autophagy and apoptosis in ALL cell models, clinical trials, and ALL animal models. Conclusions: In summary, activating autophagy and apoptosis pathways are the main strategies for ALL treatments. For ALL, combining new drugs with traditional chemotherapy and glucocorticoids treatments can achieve the greatest therapeutic effect by activating autophagy and apoptosis.

Summary: The poor prognosis and rising incidence of esophageal cancer highlight the need for improved detection and prediction methods that are essential prior to treatment. Esophageal cancer is one of the most fatal malignancies worldwide, with a dramatic increase in incidence in the Western world occurring over the past few decades. Despite improvements in the management and treatment of esophageal cancer patients, the general outcome remains very poor for overall 5-year survival rates (∼10%) and 5-year postesophagectomy survival rates (∼15–40%). Esophageal cancer is often diagnosed during its advanced stages, the main reason being the lack of early clinical symptoms. In an attempt to improve the outcome of patients after surgery, such patients are often treated with neoadjuvent concurrent chemoradiotherapy (CCRT) in order to decrease tumor size. However, CCRT may enhance toxicity levels and possibly cause a delay in surgery for patients who respond poorly to CCRT. Thus, precise biomarkers that could predict or identify patients who may or may not respond well to CCRT can assist physicians in choosing the appropriate therapy for patients. Identifying susceptible gene and biomarkers can help in predicting the treatment response of patients while improving their survival rates. Keywords: esophageal cancer, genetic factors, risk factors

Background/purpose: Fever of unknown origin (FUO) can be caused by many clinical conditions and remains a diagnostic challenge in clinical practice. The etiology of FUO varies markedly among different age groups, geographic areas, and seasons. A four-stage investigative protocol for FUO is widely applied in clinical practice. The aim of this study was to evaluate the usefulness of this four-stage protocol for identifying the etiology of FUO in children. Methods: We enrolled children younger than 18 years of age who were admitted to the Taichung Veterans General Hospital during the period from January 2006 to December 2014 with FUO persisting for more than 3 weeks. The four-stage FUO investigative guideline was used to evaluate the etiology of fever in all patients enrolled in the study. Results: The etiology of FUO was identified in 79 (84.9%) of the 93 patients enrolled in the study. The most common cause of FUO was infectious disease (37.6%), followed by malignancy (17.2%), miscellaneous disease (16.1%), and collagen vascular disease (14.0%). With respect to the four-stage survey of FUO, 36 of the 79 patients (45.6%) were identified in Stage 3, 28 patients (35.4%) in Stage 2, 13 patients (16.5%) in Stage 4, and only two patients (2.5%) in Stage 1. Conclusion: A well-designed systemic review of the epidemiological information, medical history, physical examination, laboratory analysis, and adequate invasive procedures provide adequate data to identify the most common causes of FUO in children. Keywords: children, fever of unknown origin

Background/Purpose: Deep neck infections (DNIs) often have a rapid onset and can progress to life-threatening complications. There are only a few reports on pediatric DNIs' clinical manifestations, diagnostic clues, and etiology in Taiwan. Methods: A retrospective chart review of patients (aged ≤ 18 years) diagnosed with DNI from January 2005 to December 2014 was performed. DNIs were classified into retropharyngeal, parapharyngeal, peritonsillar, submandibular, and multispace abscesses. Results: A total of 52 patients with DNI were identified. The most common site of DNI was the parapharyngeal space (n = 22, 42.3%). The most commonly associated antecedent illness was preceding upper respiratory tract infection (30.8%). The most common clinical presentation was neck mass or swelling (82.7%) and fever (75%). Pus drainage or needle aspiration was performed to obtain pus samples from the infection site for pus culture (n = 31). The most commonly isolated pathogen was Staphylococcus aureus (n = 7). Amoxicillin–clavulanic acid (56.6%) was the most commonly used antibiotics, followed by penicillin (15.1%). There was no long-term morbidity or mortality. Conclusion: When a patient (regardless of age) presents with neck mass or swelling, the DNI should always be included in the differential diagnosis. The low culture rate in Taiwan and previous partial treatment of infections may have affected identification of pathogens in cultures. Performing Gram staining and acid-fast staining of pus, instead of culture alone, as early as possible before initiating the initial antimicrobial therapy are thus crucial. The recurrence of DNI should alert the physician to the possibility of an underlying bronchogenic cyst. Excision surgery is required to cure recurrent infections.

An epidemic of influenza B/Malaysia/2506/2004 was reported in Taiwan during the 2006-2007 flu season. We investigated the flu vaccination history and clinical and laboratory characteristics of children with influenza B infection. Methods: We enrolled children younger than 18 years old who visited one of two hospitals between November 2006 and February 2007 with influenza-like illnesses. Throat swabs were taken on their first visit and cultured for viruses. Complete and differential blood counts and blood biochemical parameters were analyzed in some children. Results: Influenza virus was cultured from 51.0% of patients (101/198), 87 (86.1%) of who were infected with influenza virus type B. The remaining 14 (13.9%) were infected with influenza virus type AH3. The 87 children (median age 7.8 years) with culture- proven influenza B virus infection were enrolled. Nine parents reported that enrolled children had been vaccinated against influenza. Leukopenia was found in 56.1% (32/57) of patients, leukocytosis in 3.5% (2/57), and thrombocytopenia in 1.8% (1/57). Thirteen of 23 patients (56%) tested for creatine kinase (CK) had elevated levels (> 160 U/L), and 11 of 23 (47.8%) had myalgia associated with raised CK (p < 0.05). Twenty-six children developed complications, including one case of pneumonia with acute respiratory distress syndrome and one case of flu-associated encephalitis. Conclusion: Most children who contracted influenza B infection had not been vaccinated. Almost half the children had leukopenia, and some had leukocytosis, but thrombocytopenia was rare. There was a significant association between raised CK levels and myalgia in influenza B infection.

Background: The totally implanted vascular access device (TIVAD) is commonly used in patients with malignant tumors requiring chemotherapy or long-term intravenous infusion and those with difficulty placing peripheral venous catheters. It could also be used to draw blood in pediatric patients. Thus, how to maintain the patency and longevity of TIVAD is always emphasized. Methods: In this prospective study, TIVAD was randomly infused in patients under 18 years with three different concentrations of heparinized solutions: 10mL with 100 U/mL heparin, 20mL with 10 U/mL heparin, and 30mL with 10 U/mL heparin. Results: A total of 81 patients (46 males and 35 females) were enrolled in this study from August 2, 2013 to February 1, 2017. The mean age of those who received TIVAD implantation was 7.2 ± 5.3 years, and the mean duration of using TIVAD was 1027.6 ± 369.1 days. Patients without catheter occlusion events experienced significantly shorter hospitalizations, fewer admissions, and fewer punctures than those with catheter occlusion events (p < 0.05). The administration and frequency of blood transfusions, history of bacteremia, and medication history did not increase the risk of catheter occlusion, but puncture frequency increased this risk. In patients with catheter occlusion events (38/81, 46.9%), catheter patency was restored after instillation of urokinase solution. Conclusion: In this study, the risk of TIVAD catheter occlusion was only related to puncture frequency regardless of the heparin flush composition or patient characteristics. A high puncture frequency of TIVAD during the 3.5-year study period significantly increased the risk of catheter occlusion. Besides, flushing and locking solutions for TIVAD using heparin at 10 U/mL was effective as using heparin at 100 U/mL regardless of the flushing volume of 10, 20, or 30mL. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) infection leading to cardiopulmonary failure (CPF) is rare, but usually fatal. In such cases, intensive cardiorespiratory support is essential for survival. In this study, we report our experience in the treatment of EV71-related CPF with extracorporeal life support (ECLS). This was a retrospective study of a total of 13 children, aged 16 ± 10 months, with EV71-related hemodynamically unstable CPF, which was refractory to conventional treatments, who were rescued by transsternal ECLS from 2000 to 2008. The clinical manifestations and outcomes of the 13 children (present cohort) were compared with those of 10 children (past cohort) who had EV71-related CPF without ECLS between 1998 and 2000. Among these 13 patients, 10 were successfully weaned off ECLS and survived. The myocardial recovery time was 71 ± 28 (median, 69) h, and the ECLS duration was 93 ± 33 (median, 93) h. Six surviving patients had a good neurological outcome at hospital discharge. All surviving patients had some neurological sequelae but showed improvement at follow-up, including dysphagia in nine, central hypoventilation in seven, limb weakness in six and seizure in three. The present cohort had better neurological outcomes (46 vs. 0%, P = 0.005) and a higher survival rate (77 vs. 30%, P = 0.024) than the past cohort, respectively. Patients with EV71-related CPF supported by ECLS had a higher survival rate and fewer neurological sequelae than those who only received conventional treatments. ECLS is an effective alternative method for treatment of children with refractory EV71-related CPF. [ABSTRACT FROM AUTHOR]

The central nervous system's involvement is the most common reported extra-pulmonary manifestations of Mycoplasma pneumoniae infection, and stroke was one of the most special situations. We presented a 4-year-old child who presented with acute stroke on the third day of the onset of Mycoplasma respiratory tract infection. Brain magnetic resonance angiography demonstrated that occlusion of bilateral internal carotid arteries and vertebral arteries above the level of the first cervical vertebrate which is not been reported previously. [ABSTRACT FROM PUBLISHER]

Background: Few reports have been carried out on the characteristics of pediatric liver tumors. Methods: A retrospective study of 57 patients diagnosed with liver tumors from 1989 through 2004 was conducted. They were classified into groups; 10 benign, 33 primary malignant and 14 metastatic liver tumors. Their demographics, initial presentations, laboratory data, image findings and outcomes were investigated and compared. Results: Hepatocellular carcinoma (HCC) with 91% hepatitis B virus-related, constituted 23 of 33 primary malignant liver tumors and had the poorest survival rate. Initially, 70% of patients with primary malignant liver tumors were at disseminated stages. All of HCC and 88% of hepatoblastoma had elevated serum levels of aphal-fetoprotein. However, abnormal liver function tests as alanine aminotransferase, total bilirubin, albumin and alkaline phosphatase were uncommon in patients with pediatric liver tumors. Metastatic liver tumors compared with primary malignant liver tumors showed hypo-echogenicity in abdominal ultrasound (US) exam and a lesser presence of vessel invasion and contrast enhancement in computed tomography studies ( P < 0.01). Conclusions: It is important to diagnose primary malignant liver tumors before their clinical symptoms and signs develop. Children with chronic hepatitis B virus infection must be followed every 6 months by serum aphal-fetoprotein and abdominal US even when their liver function tests are normal. Image studies with abdominal US and computed tomography scan can differentiate between primary and metastatic liver tumors. [ABSTRACT FROM AUTHOR]

The natural course of acute immune thrombocytopenic purpura (ITP) in infants is poorly described in the literature. A retrospective study of 17 consecutive patients <1 yr of age admitted and treated for acute ITP between 1996 and 2005 was conducted. We investigated their demographics, vaccination history, clinical features, laboratory examinations, response to treatment and long-term outcome. There were 11 male and six female infants. Their ages ranged from 24 d to 12 months with a median of 3 months. All infants presented with petechiae and/or ecchymoses. Fourteen cases had platelet counts below 20 × 109/L at the time of admission. They all had good response to a single course of treatment (14/17) or multiple courses of treatment (3/17). None had progressed into chronic ITP. Seven infants had a causal relationship with immunization, five associated with hepatitis B, one diphtheria–pertussis–tetanus, one diphtheria–tetanus–acellular pertussis-inactivated poliovirus vaccine-conjugated Haemophilus influenza vaccines. These seven infants responded to treatment within 3–9 d after therapy with intravenous immunoglobulin, high-dose methylprednisolone or oral steroids. Re-boosters with vaccines revealed no recurrence of the disease in all of these seven patients. The study suggests that further immunization is not contraindicated in infants experiencing acute ITP associated with vaccines. [ABSTRACT FROM AUTHOR]

We describe 2 children with typical hand, foot, and mouth disease due to enterovirus 71 infection, 1 of whom died. Both cases were complicated by acute fulminant shock syndrome; the patients had remarkable acute left ventricular dysfunction. The clinical experience indicates that the rapid death associated with fulminant enterovirus rhombencephalitis is the result of rapid cardiogenic shock rather than neurogenic pulmonary edema. [ABSTRACT FROM AUTHOR]

Complicated skin and soft tissue infection caused by a chicken scratch has rarely been reported. A 3-year-old boy who developed haemorrhagic bullae and necrotising fasciitis following a chicken scratch is reported. Morganella morganii and enterococci were cultured from the aspirate. He received antimicrobial treatment, surgical debridement and a skin graft, and recovered uneventfully. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 4-year-old girl with recurrent meningitis. Streptococcus pneumoniae was identified from the cerebrospinal fluid (CSF). Further tests diagnosed her with Mondini dysplasia associated with pyogenic meningitis. The patient had undergone antimicrobial therapy with cefotaxime for 14 days and received surgical exploration of the right ear for two months. Surgical closure for her right middle ear was a success.

Herein we present a case of a 9-month-old boy admitted to our hospital for acute femoral osteomyelitis and hip septic arthritis treatment. Acute hepatitis with concomitant skin rash developed on the sixth day of intravenous oxacillin therapy. No other known virus- or drug-related skin eruption or hepatitis was suspected. The boy recovered completely after antibiotics were shifted to teicoplanin, and no sequelae were noted. To our knowledge, this boy is the youngest case of reported oxacillin-related hepatitis in the literatures. [ABSTRACT FROM AUTHOR]

Detailed mechanisms of WhiB-like (Wbl) proteins involved in antibiotic biosynthesis and morphological differentiation are poorly understood. Here, we characterize the role of WblAch, a Streptomyces chattanoogensis L10 protein belonging to this superfamily. Based on DNA microarray data and verified by real-time quantitative PCR (qRT-PCR), the expression of wblAch was shown to be positively regulated by AdpAch. Gel retardation assays and DNase I footprinting experiments showed that AdpAch has specific DNA-binding activity for the promoter region of wblAch. Gene disruption and genetic complementation revealed that wblAch acts in a positive manner to regulate natamycin production. When wblAch was overexpressed in the wild-type strain, the natamycin yield was increased by ~30%. This provides a strategy to generate improved strains for natamycin production. Moreover, transcriptional analysis showed that the expression levels of whi genes (including whiA, whiB, whiH, and whit) were severely depressed in the ΔwblAch mutant, suggesting that wblAch plays a part in morphological differentiation by influencing the expression of the whi genes. [ABSTRACT FROM AUTHOR]

Here we report that in Streptomyces coelicolor, the protein stability of an ECF σ factor SigT, which is involved in the negative regulation of cell differentiation, was completely dependent on its cognate anti-σ factor RstA. The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during cell differentiation. This was consistent with the delayed morphological development or secondary metabolism in the ΔclpP background after rstA deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp interaction could be disrupted by secondary metabolites, giving rise to the stabilized SigT protein and retarded morphological development in a non-antibiotic-producing mutant. Thus a novel regulatorymechanismwasrevealedthattheproteindegradationof the ECF σ factor was initiated by the degradation of its anti-σ factor, and was accelerated in a dual positive feedback manner, through regulation by secondary metabolites, to promote rapid and irreversible development of the secondary metabolism. This ingenious cooperation of intracellular components can ensure economical and exquisite control of the ECF σ factor protein level for the proper cell differentiation in Streptomyces. [ABSTRACT FROM AUTHOR]

LysR-type transcriptional regulators (LTTRs) compose a large family and are responsible for various physiological functions in bacteria, while little is understood about their regulatory mechanism on secondary metabolism in Streptomyces. Here we reported that StgR, a typical LTTR in Streptomyces coelicolor, was a negative regulator of undecylprodigiosin (Red) and γ-actinorhodin (Act) production in the early developmental phase of secondary metabolism by suppressing the expression of two pathway-specific regulator genes, redD and actll-orf4, respectively. Meanwhile, stgR expression was downregulated during secondary metabolism to remove its repressive effects on antibiotic production. Moreover, stgR expression was positively autoregulated by direct binding of StgR to its own promoter (stgRp), and the binding site adjacent to translation start codon was determined by a DNase I footprinting assay. Furthermore, the StgR-stgRp interaction could be destroyed by the antibiotic γ-actinorhodin produced from S. coelicolor. Thus, our results suggested a positive feedback regulatory mechanism of stgR expression and antibiotic production for the rapid and irreversible development of secondary metabolism in Streptomyces. [ABSTRACT FROM AUTHOR]