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Feifei Gu

Publications and source records attributed to Feifei Gu.

6 recordsLinked to original sources
PubMed2026

The inoculum effect of methicillin-susceptible Staphylococcus aureus on cefazolin and other antimicrobial agents.

UNLABELLED: The inoculum effect (IE) refers to a reduced susceptibility of methicillin-susceptible Staphylococcus aureus (MSSA) to certain antibiotics under high bacterial inocula and may contribute to treatment failure. This exploratory study assessed IE prevalence among 234 nonduplicate MSSA isolates across 11 agents spanning major therapeutic classes, including cefazolin, and characterized IE-positive clones via whole-genome sequencing to inform clinical strategies. Minimum inhibitory concentrations (MICs) were determined by broth microdilution at standard and high inocula. Whole-genome sequencing was performed on IE-positive strains to identify β-lactamase types and conduct multilocus sequence typing. The highest prevalence of IE was observed for trimethoprim-sulfamethoxazole (9.4%), followed by erythromycin (8.8%), linezolid (6.8%), penicillin (6.1%), clindamycin (5.5%), vancomycin (3.8%), cefazolin (3.0%), levofloxacin (1.5%), tetracycline (0.5%), and oxacillin and gentamicin (0.0%). All cefazolin IE-positive strains carried blaZ type A, and ST25 was the most common sequence type (42.9%). For trimethoprim-sulfamethoxazole, erythromycin, and clindamycin IE, ST7 was the most common sequence type (22.7%, 26.7%, and 33.3%, respectively). ST1281 and ST188 were the predominant sequence types among strains exhibiting linezolid IE and vancomycin IE (25.0% and 33.3%, respectively). Among the 234 MSSA strains, 66.7% of ST59, 60.0% of ST25, 58.3% of ST5, and 54.2% of ST7 strains exhibited IE to at least one antimicrobial agent. Cefazolin IE was associated with blaZ type A, and ST5, ST7, ST59, and ST25 were the major sequence types associated with IE across the antimicrobial classes tested. IMPORTANCE: Methicillin-susceptible Staphylococcus aureus (MSSA) can show an inoculum effect on multiple antimicrobial agents, which may reduce antibiotic activity under high-burden conditions. In this study, MSSA isolates from Shanghai exhibited inoculum effects on several commonly used agents, although the overall detection rates were low. Cefazolin inoculum effect was specifically associated with blaZ type A, and several major sequence types were more likely to exhibit this phenotype. These findings improve our understanding of the epidemiology of the inoculum effect in MSSA and may help guide laboratory detection and antimicrobial treatment decisions.

Cefazolin↗
PubMed2006

Assignment of a kinetic component to electron transfer between iron-sulfur clusters F(X) and F(A/B) of Photosystem I.

We studied the kinetics of reoxidation of the phylloquinones in Chlamydomonas reinhardtii Photosystem I using site-directed mutations in the PhQ(A)-binding site and of the residues serving as the axial ligand to ec3(A) and ec3(B) chlorophylls. In wild type PS I, these kinetics are biphasic, and mutations in the binding region of PhQ(A) induced a specific slowing down of the slow component. This slowing allowed detection of a previously unobserved 180-ns phase having spectral characteristics that differ from electron transfer between phylloquinones and F(X). The new kinetic phase thus reflects a different reaction that we ascribe to oxidation of F(X)(-) by the F(A/B) FeS clusters. These absorption changes partly account for the differences between the spectra associated with the two kinetic components assigned to phylloquinone reoxidation. In the mutant in which the axial ligand to ec3(A) (PsaA-Met688) was targeted, about 25% of charge separations ended in P(700)(+)A(0)(-) charge recombination; no such recombination was detected in the B-side symmetric mutant. Despite significant changes in the amplitude of the components ascribed to phylloquinone reoxidation in the two mutants, the overall nanosecond absorption changes were similar to the wild type. This suggests that these absorption changes are similar for the two different phylloquinones and that part of the differences between the decay-associated spectra of the two components reflect a contribution from different electron acceptors, i.e. from an inter-FeS cluster electron transfer.

Absorption↗
PubMed2006

Novel changes in discoidal high density lipoprotein morphology: a molecular dynamics study.

ApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95 angstroms and 78 angstroms by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules.

Apolipoprotein A-I↗
PubMed2006

Directing electron transfer within Photosystem I by breaking H-bonds in the cofactor branches.

Photosystem I has two branches of cofactors down which light-driven electron transfer (ET) could potentially proceed, each consisting of a pair of chlorophylls (Chls) and a phylloquinone (PhQ). Forward ET from PhQ to the next ET cofactor (FX) is described by two kinetic components with decay times of approximately 20 and approximately 200 ns, which have been proposed to represent ET from PhQB and PhQA, respectively. Immediately preceding each quinone is a Chl (ec3), which receives a H-bond from a nearby tyrosine. To decrease the reduction potential of each of these Chls, and thus modify the relative yield of ET within the targeted branch, this H-bond was removed by conversion of each Tyr to Phe in the green alga Chlamydomonas reinhardtii. Together, transient optical absorption spectroscopy performed in vivo and transient electron paramagnetic resonance data from thylakoid membranes showed that the mutations affect the relative amplitudes, but not the lifetimes, of the two kinetic components representing ET from PhQ to F(X). The mutation near ec3A increases the fraction of the faster component at the expense of the slower component, with the opposite effect seen in the ec3B mutant. We interpret this result as a decrease in the relative use of the targeted branch. This finding suggests that in Photosystem I, unlike type II reaction centers, the relative efficiency of the two branches is extremely sensitive to the energetics of the embedded redox cofactors.

Animals↗
PubMed2004

Mutation of the putative hydrogen-bond donor to P700 of photosystem I.

The primary electron donor of photosystem I (PS1), called P(700), is a heterodimer of chlorophyll (Chl) a and a'. The crystal structure of photosystem I reveals that the chlorophyll a' (P(A)) could be hydrogen-bonded to the protein via a threonine residue, while the chlorophyll a (P(B)) does not have such a hydrogen bond. To investigate the influence of this hydrogen bond on P(700), PsaA-Thr739 was converted to alanine to remove the H-bond to the 13(1)-keto group of the chlorophyll a' in Chlamydomonas reinhardtii. The PsaA-T739A mutant was capable of assembling active PS1. Furthermore the mutant PS1 contained approximately one chlorophyll a' molecule per reaction center, indicating that P(700) was still a Chl a/a' heterodimer in the mutant. However, the mutation induced several band shifts in the visible P(700)(+) - P(700) absorbance difference spectrum. Redox titration of P(700) revealed a 60 mV decrease in the P(700)/P(700)(+) midpoint potential of the mutant, consistent with loss of a H-bond. Fourier transform infrared (FTIR) spectroscopy indicates that the ground state of P(700) is somewhat modified by mutation of ThrA739 to alanine. Comparison of FTIR difference band shifts upon P(700)(+) formation in WT and mutant PS1 suggests that the mutation modifies the charge distribution over the pigments in the P(700)(+) state, with approximately 14-18% of the positive charge on P(B) in WT being relocated onto P(A) in the mutant. (1)H-electron-nuclear double resonance (ENDOR) analysis of the P(700)(+) cation radical was also consistent with a slight redistribution of spin from the P(B) chlorophyll to P(A), as well as some redistribution of spin within the P(B) chlorophyll. High-field electron paramagnetic resonance (EPR) spectroscopy at 330-GHz was used to resolve the g-tensor of P(700)(+), but no significant differences from wild-type were observed, except for a slight decrease of anisotropy. The mutation did, however, provoke changes in the zero-field splitting parameters of the triplet state of P(700) ((3)P(700)), as determined by EPR. Interestingly, the mutation-induced change in asymmetry of P(700) did not cause an observable change in the directionality of electron transfer within PS1.

Alanine↗